Please use this identifier to cite or link to this item:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99678Full metadata record
| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 郭靜穎 | zh_TW |
| dc.contributor.advisor | Ching-Ying Kuo | en |
| dc.contributor.author | 曾維歡 | zh_TW |
| dc.contributor.author | Weihuan Zeng Pranoto | en |
| dc.date.accessioned | 2025-09-17T16:21:04Z | - |
| dc.date.available | 2025-09-18 | - |
| dc.date.copyright | 2025-09-17 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-08-06 | - |
| dc.identifier.citation | F. Bray et al., "Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries," CA: A Cancer Journal for Clinicians, vol. 74, no. 3, pp. 229-263, 2024, doi: 10.3322/caac.21834.
衛生福利部, "111年癌症登記報告." J. Makki, "Diversity of Breast Carcinoma: Histological Subtypes and Clinical Relevance," Clinical Medicine Insights: Pathology, vol. 8, p. CPath.S31563, 2015, doi: 10.4137/CPath.S31563. S. M. Fragomeni, A. Sciallis, and J. S. Jeruss, "Molecular Subtypes and Local-Regional Control of Breast Cancer," Surg Oncol Clin N Am, vol. 27, no. 1, pp. 95-120, 2018, doi: 10.1016/j.soc.2017.08.005. R. Bradley et al., "Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials," The Lancet Oncology, vol. 23, no. 3, pp. 382-392, 2022, doi: 10.1016/S1470-2045(21)00758-0. J. F. R. Robertson, R. J. Paridaens, J. Lichfield, I. Bradbury, and C. Campbell, "Meta-analyses of phase 3 randomised controlled trials of third generation aromatase inhibitors versus tamoxifen as first-line endocrine therapy in postmenopausal women with hormone receptor-positive advanced breast cancer," European Journal of Cancer, vol. 145, pp. 19-28, 2021, doi: 10.1016/j.ejca.2020.11.038. S. M. Swain et al., "Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer," New England Journal of Medicine, vol. 372, no. 8, pp. 724-734, 2015, doi: 10.1056/NEJMoa1413513. J. Cortes et al., "Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial," The Lancet, vol. 396, no. 10265, pp. 1817-1828, 2020, doi: 10.1016/S0140-6736(20)32531-9. A. Bardia et al., "Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer," New England Journal of Medicine, vol. 384, no. 16, pp. 1529-1541, 2021, doi: 10.1056/NEJMoa2028485. M. Robson et al., "Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation," New England Journal of Medicine, vol. 377, no. 6, pp. 523-533, 2017, doi: 10.1056/NEJMoa1706450. J. K. Litton et al., "Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation," New England Journal of Medicine, vol. 379, no. 8, pp. 753-763, 2018, doi: 10.1056/NEJMoa1802905. H. Kennecke et al., "Metastatic behavior of breast cancer subtypes," J Clin Oncol, vol. 28, no. 20, pp. 3271-7, 2010, doi: 10.1200/jco.2009.25.9820. A. Dongre and R. A. Weinberg, "New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer," Nature Reviews Molecular Cell Biology, vol. 20, no. 2, pp. 69-84, 2019, doi: 10.1038/s41580-018-0080-4. K. Vuoriluoto et al., "Vimentin regulates EMT induction by Slug and oncogenic H-Ras and migration by governing Axl expression in breast cancer," Oncogene, vol. 30, no. 12, pp. 1436-1448, 2011, doi: 10.1038/onc.2010.509. S. R. McKeown, "Defining normoxia, physoxia and hypoxia in tumours-implications for treatment response," Br J Radiol, vol. 87, no. 1035, p. 20130676, 2014, doi: 10.1259/bjr.20130676. J. W. Kim, I. Tchernyshyov, G. L. Semenza, and C. V. Dang, "HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia," Cell Metab, vol. 3, no. 3, pp. 177-85, 2006, doi: 10.1016/j.cmet.2006.02.002. I. Papandreou, R. A. Cairns, L. Fontana, A. L. Lim, and N. C. Denko, "HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption," Cell Metab, vol. 3, no. 3, pp. 187-97, 2006, doi: 10.1016/j.cmet.2006.01.012. N. V. Iyer et al., "Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha," Genes Dev, vol. 12, no. 2, pp. 149-62, 1998, doi: 10.1101/gad.12.2.149. Q. Shi, J. L. Abbruzzese, S. Huang, I. J. Fidler, Q. Xiong, and K. Xie, "Constitutive and Inducible Interleukin 8 Expression by Hypoxia and Acidosis Renders Human Pancreatic Cancer Cells More Tumorigenic and Metastatic," Clinical Cancer Research, vol. 5, no. 11, pp. 3711-3721, 1999. A. Hirayama et al., "Quantitative Metabolome Profiling of Colon and Stomach Cancer Microenvironment by Capillary Electrophoresis Time-of-Flight Mass Spectrometry," Cancer Research, vol. 69, no. 11, pp. 4918-4925, 2009, doi: 10.1158/0008-5472.Can-08-4806. M. Pan et al., "Regional glutamine deficiency in tumours promotes dedifferentiation through inhibition of histone demethylation," Nature Cell Biology, vol. 18, no. 10, pp. 1090-1101, 2016, doi: 10.1038/ncb3410. M. Buzzai et al., "The glucose dependence of Akt-transformed cells can be reversed by pharmacologic activation of fatty acid beta-oxidation," Oncogene, vol. 24, no. 26, pp. 4165-73, 2005, doi: 10.1038/sj.onc.1208622. J. R. Mayers et al., "Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers," Science, vol. 353, no. 6304, pp. 1161-5, 2016, doi: 10.1126/science.aaf5171. I. M. Ahmad et al., "Mitochondrial O2*- and H2O2 mediate glucose deprivation-induced stress in human cancer cells," J Biol Chem, vol. 280, no. 6, pp. 4254-63, 2005, doi: 10.1074/jbc.M411662200. S. M. Hong et al., "NAMPT suppresses glucose deprivation-induced oxidative stress by increasing NADPH levels in breast cancer," Oncogene, vol. 35, no. 27, pp. 3544-3554, 2016, doi: 10.1038/onc.2015.415. H. Endo, S. Owada, Y. Inagaki, Y. Shida, and M. Tatemichi, "Glucose starvation induces LKB1-AMPK-mediated MMP-9 expression in cancer cells," Scientific Reports, vol. 8, no. 1, p. 10122, 2018, doi: 10.1038/s41598-018-28074-w. P. Paoli, E. Giannoni, and P. Chiarugi, "Anoikis molecular pathways and its role in cancer progression," Biochim Biophys Acta, vol. 1833, no. 12, pp. 3481-3498, 2013, doi: 10.1016/j.bbamcr.2013.06.026. S. Frisch and H. Francis, "Disruption of epithelial cell-matrix interactions induces apoptosis," Journal of Cell Biology, vol. 124, no. 4, pp. 619-626, 1994, doi: 10.1083/jcb.124.4.619. A. D. Weems et al., "Blebs promote cell survival by assembling oncogenic signalling hubs," Nature, vol. 615, no. 7952, pp. 517-525, 2023, doi: 10.1038/s41586-023-05758-6. B. C. Luey and F. E. B. May, "Insulin-like growth factors are essential to prevent anoikis in oestrogen-responsive breast cancer cells: importance of the type I IGF receptor and PI3-kinase/Akt pathway," Molecular Cancer, vol. 15, no. 1, p. 8, 2016, doi: 10.1186/s12943-015-0482-2. L. Wei, Y. Yang, X. Zhang, and Q. Yu, "Altered regulation of Src upon cell detachment protects human lung adenocarcinoma cells from anoikis," Oncogene, vol. 23, no. 56, pp. 9052-9061, 2004, doi: 10.1038/sj.onc.1208091. S. M. Janes and F. M. Watt "Switch from αvβ5 to αvβ6 integrin expression protects squamous cell carcinomas from anoikis," Journal of Cell Biology, vol. 166, no. 3, pp. 419-431, 2004, doi: 10.1083/jcb.200312074. D. M. Ramos et al., "Expression of integrin beta 6 enhances invasive behavior in oral squamous cell carcinoma," Matrix Biol, vol. 21, no. 3, pp. 297-307, 2002, doi: 10.1016/s0945-053x(02)00002-1. M. Haemmerle et al., "Platelets reduce anoikis and promote metastasis by activating YAP1 signaling," Nature Communications, vol. 8, no. 1, p. 310, 2017, doi: 10.1038/s41467-017-00411-z. X. Chen et al., "Shear stress enhances anoikis resistance of cancer cells through ROS and NO suppressed degeneration of Caveolin-1," Free Radic Biol Med, vol. 193, no. Pt 1, pp. 95-107, 2022, doi: 10.1016/j.freeradbiomed.2022.10.271. Z. T. Schafer et al., "Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment," Nature, vol. 461, no. 7260, pp. 109-13, 2009, doi: 10.1038/nature08268. S. Kamarajugadda et al., "Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis," Cell Death & Disease, vol. 4, no. 2, pp. e504-e504, 2013, doi: 10.1038/cddis.2013.20. T. L. Ng et al., "The AMPK stress response pathway mediates anoikis resistance through inhibition of mTOR and suppression of protein synthesis," Cell Death Differ, vol. 19, no. 3, pp. 501-10, 2012, doi: 10.1038/cdd.2011.119. C. Fung, R. Lock, S. Gao, E. Salas, and J. Debnath, "Induction of autophagy during extracellular matrix detachment promotes cell survival," Mol Biol Cell, vol. 19, no. 3, pp. 797-806, 2008, doi: 10.1091/mbc.e07-10-1092. R. Guo et al., "Multifaceted regulatory mechanisms of the EGR family in tumours and prospects for therapeutic applications (Review)," Int J Mol Med, vol. 56, no. 1, p. 113, 2025, doi: 10.3892/ijmm.2025.5554. B. Christy and D. Nathans, "DNA binding site of the growth factor-inducible protein Zif268," Proc Natl Acad Sci U S A, vol. 86, no. 22, pp. 8737-41, 1989, doi: 10.1073/pnas.86.22.8737. P. Topilko et al., "Krox-20 controls myelination in the peripheral nervous system," Nature, vol. 371, no. 6500, pp. 796-9, 1994, doi: 10.1038/371796a0. L. Li et al., "Egr3, a synaptic activity regulated transcription factor that is essential for learning and memory," Mol Cell Neurosci, vol. 35, no. 1, pp. 76-88, 2007, doi: 10.1016/j.mcn.2007.02.004. W. G. Tourtellotte, R. Nagarajan, A. Auyeung, C. Mueller, and J. Milbrandt, "Infertility associated with incomplete spermatogenic arrest and oligozoospermia in Egr4-deficient mice," Development, vol. 126, no. 22, pp. 5061-71, 1999, doi: 10.1242/dev.126.22.5061. J. Milbrandt, "A nerve growth factor-induced gene encodes a possible transcriptional regulatory factor," Science, vol. 238, no. 4828, pp. 797-9, 1987, doi: 10.1126/science.3672127. V. P. Sukhatme et al., "A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization," Cell, vol. 53, no. 1, pp. 37-43, 1988, doi: 10.1016/0092-8674(88)90485-0. R. W. Lim, B. C. Varnum, and H. R. Herschman, "Cloning of tetradecanoyl phorbol ester-induced 'primary response' sequences and their expression in density-arrested Swiss 3T3 cells and a TPA non-proliferative variant," Oncogene, vol. 1, no. 3, pp. 263-70, 1987. B. A. Christy, L. F. Lau, and D. Nathans, "A gene activated in mouse 3T3 cells by serum growth factors encodes a protein with "zinc finger" sequences," Proc Natl Acad Sci U S A, vol. 85, no. 21, pp. 7857-61, 1988, doi: 10.1073/pnas.85.21.7857. P. Lemaire, O. Revelant, R. Bravo, and P. Charnay, "Two mouse genes encoding potential transcription factors with identical DNA-binding domains are activated by growth factors in cultured cells," Proceedings of the National Academy of Sciences, vol. 85, no. 13, pp. 4691-4695, 1988, doi: 10.1073/pnas.85.13.4691. X. Cao, R. Mahendran, G. R. Guy, and Y. H. Tan, "Detection and characterization of cellular EGR-1 binding to its recognition site," Journal of Biological Chemistry, vol. 268, no. 23, pp. 16949-16957, 1993, doi: 10.1016/S0021-9258(19)85286-9. E. Havis and D. Duprez, "EGR1 Transcription Factor is a Multifaceted Regulator of Matrix Production in Tendons and Other Connective Tissues," International Journal of Molecular Sciences, vol. 21, no. 5, p. 1664, 2020, doi: 10.3390/ijms21051664. J. L. Schwachtgen, P. Houston, C. Campbell, V. Sukhatme, and M. Braddock, "Fluid shear stress activation of egr-1 transcription in cultured human endothelial and epithelial cells is mediated via the extracellular signal-related kinase 1/2 mitogen-activated protein kinase pathway," J Clin Invest, vol. 101, no. 11, pp. 2540-9, 1998, doi: 10.1172/jci1404. C. P. Lim, N. Jain, and X. Cao, "Stress-induced immediate-early gene, egr-1, involves activation of p38/JNK1," Oncogene, vol. 16, no. 22, pp. 2915-26, 1998, doi: 10.1038/sj.onc.1201834. L. Hao et al., "The Role of Early Growth Response Family Members 1-4 in Prognostic Value of Breast Cancer," Frontiers in Genetics, Original Research vol. 12, 2021, doi: 10.3389/fgene.2021.680132. L. Chen et al., "Identification of early growth response protein 1 (EGR-1) as a novel target for JUN-induced apoptosis in multiple myeloma," Blood, vol. 115, no. 1, pp. 61-70, 2010, doi: 10.1182/blood-2009-03-210526. H. Zhang et al., "EGR1 decreases the malignancy of human non-small cell lung carcinoma by regulating KRT18 expression," Scientific Reports, vol. 4, no. 1, p. 5416, 2014, doi: 10.1038/srep05416. Y. Wang et al., "EGR1 induces EMT in pancreatic cancer via a P300/SNAI2 pathway," J Transl Med, vol. 21, no. 1, p. 201, 2023, doi: 10.1186/s12967-023-04043-4. T. Sun, H. Tian, Y. G. Feng, Y. Q. Zhu, and W. Q. Zhang, "Egr-1 promotes cell proliferation and invasion by increasing β-catenin expression in gastric cancer," Dig Dis Sci, vol. 58, no. 2, pp. 423-30, 2013, doi: 10.1007/s10620-012-2356-4. S. K. Saha et al., "Prognostic role of EGR1 in breast cancer: a systematic review," BMB Rep, vol. 54, no. 10, pp. 497-504, 2021, doi: 10.5483/BMBRep.2021.54.10.087. L. L. Wei, X. J. Wu, C. C. Gong, and D. S. Pei, "Egr-1 suppresses breast cancer cells proliferation by arresting cell cycle progression via down-regulating CyclinDs," Int J Clin Exp Pathol, vol. 10, no. 10, pp. 10212-10222, 2017. K. M. Wong, J. Song, and Y. H. Wong, "CTCF and EGR1 suppress breast cancer cell migration through transcriptional control of Nm23-H1," Scientific Reports, vol. 11, no. 1, p. 491, 2021, doi: 10.1038/s41598-020-79869-9. E. Jung, Y. H. Lee, S. Ou, T. Y. Kim, and S. Y. Shin, "EGR1 Regulation of Vasculogenic Mimicry in the MDA-MB-231 Triple-Negative Breast Cancer Cell Line through the Upregulation of KLF4 Expression," Int J Mol Sci, vol. 24, no. 18, 2023, doi: 10.3390/ijms241814375. T. Tang et al., "Protease Nexin I is a feedback regulator of EGF/PKC/MAPK/EGR1 signaling in breast cancer cells metastasis and stemness," Cell Death & Disease, vol. 10, no. 9, p. 649, 2019, doi: 10.1038/s41419-019-1882-9. X. Cao, R. Mahendran, G. R. Guy, and Y. H. Tan, "Protein phosphatase inhibitors induce the sustained expression of the Egr-1 gene and the hyperphosphorylation of its gene product," J Biol Chem, vol. 267, no. 18, pp. 12991-7, 1992, doi: 10.1016/S0021-9258(18)42372-1. J. Yu et al., "PTEN regulation by Akt-EGR1-ARF-PTEN axis," Embo j, vol. 28, no. 1, pp. 21-33, 2009, doi: 10.1038/emboj.2008.238. A. G. Manente, G. Pinton, D. Tavian, G. Lopez-Rodas, E. Brunelli, and L. Moro, "Coordinated sumoylation and ubiquitination modulate EGF induced EGR1 expression and stability," PLoS One, vol. 6, no. 10, p. e25676, 2011, doi: 10.1371/journal.pone.0025676. N. Jain, R. Mahendran, R. Philp, G. R. Guy, Y. H. Tan, and X. Cao, "Casein kinase II associates with Egr-1 and acts as a negative modulator of its DNA binding and transcription activities in NIH 3T3 cells," J Biol Chem, vol. 271, no. 23, pp. 13530-6, 1996, doi: 10.1074/jbc.271.23.13530. J. Yu, I. de Belle, H. Liang, and E. D. Adamson, "Coactivating factors p300 and CBP are transcriptionally crossregulated by Egr1 in prostate cells, leading to divergent responses," Mol Cell, vol. 15, no. 1, pp. 83-94, 2004, doi: 10.1016/j.molcel.2004.06.030. F. S. Santiago, E. Sanchez-Guerrero, G. Zhang, L. Zhong, M. J. Raftery, and L. M. Khachigian, "Extracellular signal-regulated kinase-1 phosphorylates early growth response-1 at serine 26," Biochemical and Biophysical Research Communications, vol. 510, no. 3, pp. 345-351, 2019, doi: 10.1016/j.bbrc.2019.01.019. F. S. Santiago, Y. Li, and L. M. Khachigian, "Serine 26 in Early Growth Response-1 Is Critical for Endothelial Proliferation, Migration, and Network Formation," J Am Heart Assoc, vol. 10, no. 18, p. e020521, 2021, doi: 10.1161/jaha.120.020521. J. Zhou et al., "JNK-dependent phosphorylation and nuclear translocation of EGR-1 promotes cardiomyocyte apoptosis," Apoptosis, vol. 27, no. 3-4, pp. 246-260, 2022, doi: 10.1007/s10495-022-01714-3. Z. J. Waldrip et al., "DNA-PKcs kinase activity stabilizes the transcription factor Egr1 in activated immune cells," J Biol Chem, vol. 297, no. 4, p. 101209, 2021, doi: 10.1016/j.jbc.2021.101209. N. GRANKOWSKI, B. BOLDYREFF, and O.-G. ISSINGER, "Isolation and characterization of recombinant human casein kinase II subunits α and β from bacteria," European Journal of Biochemistry, vol. 198, no. 1, pp. 25-30, 1991, doi: 10.1111/j.1432-1033.1991.tb15982.x. F. MEGGIO, B. BOLDYREFF, O. MARIN, L. A. PINNA, and O.-G. ISSINGER, "Role of the β subunit of casein kinase-2 on the stability and specificity of the recombinant reconstituted holoenzyme," European Journal of Biochemistry, vol. 204, no. 1, pp. 293-297, 1992, doi: 10.1111/j.1432-1033.1992.tb16636.x. G. Burnett and E. P. Kennedy, "THE ENZYMATIC PHOSPHORYLATION OF PROTEINS," Journal of Biological Chemistry, vol. 211, no. 2, pp. 969-980, 1954, doi: 10.1016/S0021-9258(18)71184-8. L. A. Pinna, "A historical view of protein kinase CK2," Cell Mol Biol Res, vol. 40, no. 5-6, pp. 383-90, 1994. G. Di Maira et al., "Protein kinase CK2 phosphorylates and upregulates Akt/PKB," Cell Death & Differentiation, vol. 12, no. 6, pp. 668-677, 2005, doi: 10.1038/sj.cdd.4401604. G. Di Maira, F. Brustolon, L. A. Pinna, and M. Ruzzene, "Dephosphorylation and inactivation of Akt/PKB is counteracted by protein kinase CK2 in HEK 293T cells," Cell Mol Life Sci, vol. 66, no. 20, pp. 3363-73, 2009, doi: 10.1007/s00018-009-0108-1. Y. Miyata and E. Nishida, "CK2 controls multiple protein kinases by phosphorylating a kinase-targeting molecular chaperone, Cdc37," Mol Cell Biol, vol. 24, no. 9, pp. 4065-74, 2004, doi: 10.1128/mcb.24.9.4065-4074.2004. E. Alcaraz et al., "Effects of CK2β subunit down-regulation on Akt signalling in HK-2 renal cells," PLoS One, vol. 15, no. 1, p. e0227340, 2020, doi: 10.1371/journal.pone.0227340. A. Siddiqui-Jain et al., "CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy," Cancer Res, vol. 70, no. 24, pp. 10288-98, 2010, doi: 10.1158/0008-5472.Can-10-1893. B. Guerra, "Protein kinase CK2 subunits are positive regulators of AKT kinase," Int J Oncol, vol. 28, no. 3, pp. 685-693, 2006, doi: 10.3892/ijo.28.3.685. C. E. Ortega, Y. Seidner, and I. Dominguez, "Mining CK2 in cancer," PLoS One, vol. 9, no. 12, p. e115609, 2014, doi: 10.1371/journal.pone.0115609. R. Hamacher, D. Saur, R. Fritsch, M. Reichert, R. M. Schmid, and G. Schneider, "Casein kinase II inhibition induces apoptosis in pancreatic cancer cells," Oncol Rep, vol. 18, no. 3, pp. 695-701, 2007, doi: 10.3892/or.18.3.695. K. Takahashi et al., "Inhibition of casein kinase 2 prevents growth of human osteosarcoma," Oncol Rep, vol. 37, no. 2, pp. 1141-1147, 2017, doi: 10.3892/or.2016.5310. G. Di Maira et al., "Pharmacological inhibition of protein kinase CK2 reverts the multidrug resistance phenotype of a CEM cell line characterized by high CK2 level," Oncogene, vol. 26, no. 48, pp. 6915-6926, 2007, doi: 10.1038/sj.onc.1210495. M. Ruzzene and L. A. Pinna, "Addiction to protein kinase CK2: a common denominator of diverse cancer cells?," Biochim Biophys Acta, vol. 1804, no. 3, pp. 499-504, 2010, doi: 10.1016/j.bbapap.2009.07.018. J. Han, J.-D. Lee, L. Bibbs, and R. J. Ulevitch, "A MAP Kinase Targeted by Endotoxin and Hyperosmolarity in Mammalian Cells," Science, vol. 265, no. 5173, pp. 808-811, 1994, doi: 10.1126/science.7914033. J. C. Lee et al., "A protein kinase involved in the regulation of inflammatory cytokine biosynthesis," Nature, vol. 372, no. 6508, pp. 739-46, 1994, doi: 10.1038/372739a0. N. W. Freshney et al., "Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27," Cell, vol. 78, no. 6, pp. 1039-49, 1994, doi: 10.1016/0092-8674(94)90278-x. J. Rouse et al., "A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins," Cell, vol. 78, no. 6, pp. 1027-37, 1994, doi: 10.1016/0092-8674(94)90277-1. J. Raingeaud et al., "Pro-inflammatory Cytokines and Environmental Stress Cause p38 Mitogen-activated Protein Kinase Activation by Dual Phosphorylation on Tyrosine and Threonine (∗)," Journal of Biological Chemistry, vol. 270, no. 13, pp. 7420-7426, 1995, doi: 10.1074/jbc.270.13.7420. C. T. Cheng et al., "Metabolic Stress-Induced Phosphorylation of KAP1 Ser473 Blocks Mitochondrial Fusion in Breast Cancer Cells," Cancer Res, vol. 76, no. 17, pp. 5006-18, 2016, doi: 10.1158/0008-5472.Can-15-2921. S. Wei et al., "GFAT1-linked TAB1 glutamylation sustains p38 MAPK activation and promotes lung cancer cell survival under glucose starvation," Cell Discovery, vol. 8, no. 1, p. 77, 2022, doi: 10.1038/s41421-022-00423-0. Z. Li, C. M. Chang, L. Wang, P. Zhang, and H. G. Shu, "Cyclooxygenase-2 Induction by Amino Acid Deprivation Requires p38 Mitogen-Activated Protein Kinase in Human Glioma Cells," Cancer Invest, vol. 35, no. 4, pp. 237-247, 2017, doi: 10.1080/07357907.2017.1292517. L. Xu, P. S. Pathak, and D. Fukumura, "Hypoxia-Induced Activation of p38 Mitogen-Activated Protein Kinase and Phosphatidylinositol 3’-Kinase Signaling Pathways Contributes to Expression of Interleukin 8 in Human Ovarian Carcinoma Cells," Clinical Cancer Research, vol. 10, no. 2, pp. 701-707, 2004, doi: 10.1158/1078-0432.Ccr-0953-03. D. M. Owens and S. M. Keyse, "Differential regulation of MAP kinase signalling by dual-specificity protein phosphatases," Oncogene, vol. 26, no. 22, pp. 3203-3213, 2007, doi: 10.1038/sj.onc.1210412. Y.-Y. Zhang, Z.-Q. Mei, J.-W. Wu, and Z.-X. Wang, "Enzymatic Activity and Substrate Specificity of Mitogen-activated Protein Kinase p38α in Different Phosphorylation States*," Journal of Biological Chemistry, vol. 283, no. 39, pp. 26591-26601, 2008, doi: 10.1074/jbc.M801703200. K. Pakos‐Zebrucka, I. Koryga, K. Mnich, M. Ljujic, A. Samali, and A. M. Gorman, "The integrated stress response," EMBO reports, vol. 17, no. 10, pp. 1374-1395, 2016, doi: 10.15252/embr.201642195. I. Roussou, G. Thireos, and B. M. Hauge, "Transcriptional-translational regulatory circuit in Saccharomyces cerevisiae which involves the GCN4 transcriptional activator and the GCN2 protein kinase," Mol Cell Biol, vol. 8, no. 5, pp. 2132-9, 1988, doi: 10.1128/mcb.8.5.2132-2139.1988. S. A. Wek, Z. Shuhao, and R. C. and Wek, "The Histidyl-tRNA Synthetase-Related Sequence in the eIF-2α Protein Kinase GCN2 Interacts with tRNA and Is Required for Activation in Response to Starvation for Different Amino Acids," Molecular and Cellular Biology, vol. 15, no. 8, pp. 4497-4506, 1995, doi: 10.1128/MCB.15.8.4497. P. R. Romano et al., "Autophosphorylation in the Activation Loop Is Required for Full Kinase Activity In Vivo of Human and Yeast Eukaryotic Initiation Factor 2α Kinases PKR and GCN2," Molecular and Cellular Biology, vol. 18, no. 4, pp. 2282-2297, 1998, doi: 10.1128/MCB.18.4.2282. Y. Wang et al., "Amino acid deprivation promotes tumor angiogenesis through the GCN2/ATF4 pathway," Neoplasia, vol. 15, no. 8, pp. 989-97, 2013, doi: 10.1593/neo.13262. J. Ye et al., "The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation," Embo j, vol. 29, no. 12, pp. 2082-96, 2010, doi: 10.1038/emboj.2010.81. Y.-Z. Wu, Y.-H. Chen, C.-T. Cheng, D. K. Ann, and C.-Y. Kuo, "Amino acid restriction induces a long non-coding RNA UBA6-AS1 to regulate GCN2-mediated integrated stress response in breast cancer," The FASEB Journal, vol. 36, no. 3, p. e22201, 2022, doi: 10.1096/fj.202101466R. R. Yang, S. A. Wek, and R. C. Wek, "Glucose limitation induces GCN4 translation by activation of Gcn2 protein kinase," Mol Cell Biol, vol. 20, no. 8, pp. 2706-17, 2000, doi: 10.1128/mcb.20.8.2706-2717.2000. S. Shin et al., "ERK2 Mediates Metabolic Stress Response to Regulate Cell Fate," Molecular Cell, vol. 59, no. 3, pp. 382-398, 2015, doi: 10.1016/j.molcel.2015.06.020. D. Carling, V. A. Zammit, and D. G. Hardie, "A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis," FEBS Letters, vol. 223, no. 2, pp. 217-222, 1987, doi: 10.1016/0014-5793(87)80292-2. I. P. Salt, G. Johnson, S. J. Ashcroft, and D. G. Hardie, "AMP-activated protein kinase is activated by low glucose in cell lines derived from pancreatic beta cells, and may regulate insulin release," Biochem J, vol. 335 ( Pt 3), no. Pt 3, pp. 533-9, 1998, doi: 10.1042/bj3350533. C.-S. Zhang et al., "Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK," Nature, vol. 548, no. 7665, pp. 112-116, 2017, doi: 10.1038/nature23275. K. R. Laderoute et al., "5’-AMP-Activated Protein Kinase (AMPK) Is Induced by Low-Oxygen and Glucose Deprivation Conditions Found in Solid-Tumor Microenvironments," Molecular and Cellular Biology, vol. 26, no. 14, pp. 5336-5347, 2006, doi: 10.1128/MCB.00166-06. J. M. Corton, J. G. Gillespie, and D. G. Hardie, "Role of the AMP-activated protein kinase in the cellular stress response," Current Biology, vol. 4, no. 4, pp. 315-324, 1994, doi: 10.1016/S0960-9822(00)00070-1. X. Li et al., "Structural basis of AMPK regulation by adenine nucleotides and glycogen," Cell Research, vol. 25, no. 1, pp. 50-66, 2015, doi: 10.1038/cr.2014.150. S. P. Davies, N. R. Helps, P. T. Cohen, and D. G. Hardie, "5'-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC," FEBS Lett, vol. 377, no. 3, pp. 421-5, 1995, doi: 10.1016/0014-5793(95)01368-7. S. C. Stein, A. Woods, N. A. Jones, M. D. Davison, and D. Carling, "The regulation of AMP-activated protein kinase by phosphorylation," Biochem J, vol. 345 Pt 3, no. Pt 3, pp. 437-43, 2000. S. A. Hawley et al., "Characterization of the AMP-activated Protein Kinase Kinase from Rat Liver and Identification of Threonine 172 as the Major Site at Which It Phosphorylates AMP-activated Protein Kinase*," Journal of Biological Chemistry, vol. 271, no. 44, pp. 27879-27887, 1996, doi: 10.1074/jbc.271.44.27879. A. Woods et al., "LKB1 is the upstream kinase in the AMP-activated protein kinase cascade," Curr Biol, vol. 13, no. 22, pp. 2004-8, 2003, doi: 10.1016/j.cub.2003.10.031. A. Woods et al., "Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells," Cell Metab, vol. 2, no. 1, pp. 21-33, 2005, doi: 10.1016/j.cmet.2005.06.005. R. J. Shaw et al., "The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress," Proc Natl Acad Sci U S A, vol. 101, no. 10, pp. 3329-35, 2004, doi: 10.1073/pnas.0308061100. S. A. Hawley et al., "Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade," J Biol, vol. 2, no. 4, p. 28, 2003, doi: 10.1186/1475-4924-2-28. S. W. Lee et al., "Skp2-dependent ubiquitination and activation of LKB1 is essential for cancer cell survival under energy stress," Mol Cell, vol. 57, no. 6, pp. 1022-1033, 2015, doi: 10.1016/j.molcel.2015.01.015. M. Yuan et al., "CARS senses cysteine deprivation to activate AMPK for cell survival," Embo j, vol. 40, no. 21, p. e108028, 2021, doi: 10.15252/embj.2021108028. G. Ghislat, M. Patron, R. Rizzuto, and E. Knecht, "Withdrawal of essential amino acids increases autophagy by a pathway involving Ca2+/calmodulin-dependent kinase kinase-β (CaMKK-β)," J Biol Chem, vol. 287, no. 46, pp. 38625-36, 2012, doi: 10.1074/jbc.M112.365767. P. T. Mungai et al., "Hypoxia triggers AMPK activation through reactive oxygen species-mediated activation of calcium release-activated calcium channels," Mol Cell Biol, vol. 31, no. 17, pp. 3531-45, 2011, doi: 10.1128/mcb.05124-11. A. Sundararaman, U. Amirtham, and A. Rangarajan, "Calcium-Oxidant Signaling Network Regulates AMP-activated Protein Kinase (AMPK) Activation upon Matrix Deprivation," J Biol Chem, vol. 291, no. 28, pp. 14410-29, 2016, doi: 10.1074/jbc.M116.731257. J. Ha, S. Daniel, S. S. Broyles, and K. H. Kim, "Critical phosphorylation sites for acetyl-CoA carboxylase activity," Journal of Biological Chemistry, vol. 269, no. 35, pp. 22162-22168, 1994, doi: 10.1016/S0021-9258(17)31770-2. K. Inoki, T. Zhu, and K.-L. Guan, "TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival," Cell, vol. 115, no. 5, pp. 577-590, 2003, doi: 10.1016/S0092-8674(03)00929-2. D. M. Gwinn et al., "AMPK phosphorylation of raptor mediates a metabolic checkpoint," Mol Cell, vol. 30, no. 2, pp. 214-26, 2008, doi: 10.1016/j.molcel.2008.03.003. J. Kim, M. Kundu, B. Viollet, and K.-L. Guan, "AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1," Nature Cell Biology, vol. 13, no. 2, pp. 132-141, 2011, doi: 10.1038/ncb2152. A. C. Ferretti et al., "Metformin and glucose starvation decrease the migratory ability of hepatocellular carcinoma cells: targeting AMPK activation to control migration," Scientific Reports, vol. 9, no. 1, p. 2815, 2019, doi: 10.1038/s41598-019-39556-w. T. Fodor et al., "Combined Treatment of MCF-7 Cells with AICAR and Methotrexate, Arrests Cell Cycle and Reverses Warburg Metabolism through AMP-Activated Protein Kinase (AMPK) and FOXO1," PLoS One, vol. 11, no. 2, p. e0150232, 2016, doi: 10.1371/journal.pone.0150232. K. Kato et al., "Critical roles of AMP-activated protein kinase in constitutive tolerance of cancer cells to nutrient deprivation and tumor formation," Oncogene, vol. 21, no. 39, pp. 6082-90, 2002, doi: 10.1038/sj.onc.1205737. M.-J. Kim et al., "AMP-activated Protein Kinase Antagonizes Pro-apoptotic Extracellular Signal-regulated Kinase Activation by Inducing Dual-specificity Protein Phosphatases in Response to Glucose Deprivation in HCT116 Carcinoma*," Journal of Biological Chemistry, vol. 285, no. 19, pp. 14617-14627, 2010, doi: 10.1074/jbc.M109.085456. 劉格均, "探討 EGR1 在代謝壓力下對於乳癌細胞的作用," 碩士, 醫學檢驗暨生物技術學研究所, 國立臺灣大學, 2021. 雷善婷, "探討在乳癌代謝壓力反應中EGR1的轉譯後修飾對其功能之影響," 碩士, 醫學檢驗暨生物技術學系, 國立臺灣大學, 2023. Y. Yu et al., "CircCEMIP promotes anoikis-resistance by enhancing protective autophagy in prostate cancer cells," Journal of Experimental & Clinical Cancer Research, vol. 41, no. 1, p. 188, 2022, doi: 10.1186/s13046-022-02381-7. B. T. Kren et al., "Preclinical evaluation of cyclin dependent kinase 11 and casein kinase 2 survival kinases as RNA interference targets for triple negative breast cancer therapy," Breast Cancer Research, vol. 17, no. 1, p. 19, 2015, doi: 10.1186/s13058-015-0524-0. S.-Y. J. a. S.-Y. Im, "Estrogen Induces CK2α Activation via Generation of Reactive Oxygen Species," Biomedical Science Letters, vol. 25, no. 1, pp. 23-31, 2019, doi: 10.15616/BSL.2019.25.1.23. M. Sayed, S. O. Kim, B. S. Salh, O.-G. Issinger, and S. L. Pelech, "Stress-induced Activation of Protein Kinase CK2 by Direct Interaction with p38 Mitogen-activated Protein Kinase*," Journal of Biological Chemistry, vol. 275, no. 22, pp. 16569-16573, 2000, doi: 10.1074/jbc.M000312200. C. M. Woodson and K. Kehn-Hall, "Examining the role of EGR1 during viral infections," Front Microbiol, vol. 13, p. 1020220, 2022, doi: 10.3389/fmicb.2022.1020220. I. de Belle, R. P. Huang, Y. Fan, C. Liu, D. Mercola, and E. D. Adamson, "p53 and Egr-1 additively suppress transformed growth in HT1080 cells but Egr-1 counteracts p53-dependent apoptosis," Oncogene, vol. 18, no. 24, pp. 3633-42, 1999, doi: 10.1038/sj.onc.1202696. R. P. Huang and E. D. Adamson, "The phosphorylated forms of the transcription factor, Egr-1, bind to DNA more efficiently than non-phosphorylated," Biochem Biophys Res Commun, vol. 200, no. 3, pp. 1271-6, 1994, doi: 10.1006/bbrc.1994.1588. S. L. Choi et al., "The regulation of AMP-activated protein kinase by H(2)O(2)," Biochem Biophys Res Commun, vol. 287, no. 1, pp. 92-7, 2001, doi: 10.1006/bbrc.2001.5544. S. A. Hawley et al., "Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation," Cell Metab, vol. 11, no. 6, pp. 554-65, 2010, doi: 10.1016/j.cmet.2010.04.001. J. W. Zmijewski, S. Banerjee, H. Bae, A. Friggeri, E. R. Lazarowski, and E. Abraham, "Exposure to hydrogen peroxide induces oxidation and activation of AMP-activated protein kinase," J Biol Chem, vol. 285, no. 43, pp. 33154-33164, 2010, doi: 10.1074/jbc.M110.143685. H. R. Christofk et al., "The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth," Nature, vol. 452, no. 7184, pp. 230-233, 2008, doi: 10.1038/nature06734. C. Ma et al., "Knockdown of Pyruvate Kinase M Inhibits Cell Growth and Migration by Reducing NF-κB Activity in Triple-Negative Breast Cancer Cells," Molecules and Cells, vol. 42, no. 9, pp. 628-636, 2019, doi: 10.14348/molcells.2019.0038. H. Xiao et al., "PKM2 Promotes Breast Cancer Progression by Regulating Epithelial Mesenchymal Transition," Analytical Cellular Pathology, vol. 2020, no. 1, p. 8396023, 2020, doi: 10.1155/2020/8396023. W. Yang et al., "ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect," Nature Cell Biology, vol. 14, no. 12, pp. 1295-1304, 2012, doi: 10.1038/ncb2629. M. R. Pandkar et al., "PKM2 dictates the poised chromatin state of PFKFB3 promoter to enhance breast cancer progression," NAR Cancer, vol. 5, no. 3, 2023, doi: 10.1093/narcan/zcad032. Y.-C. Yang et al., "Nuclear translocation of PKM2/AMPK complex sustains cancer stem cell populations under glucose restriction stress," Cancer Letters, vol. 421, pp. 28-40, 2018, doi: 10.1016/j.canlet.2018.01.075. Y.-F. Wu, H.-K. Wang, H.-W. Chang, J. Sun, J.-S. Sun, and Y.-H. Chao, "High glucose alters tendon homeostasis through downregulation of the AMPK/Egr1 pathway," Scientific Reports, vol. 7, no. 1, p. 44199, 2017, doi: 10.1038/srep44199. S. S. Hann, Q. Tang, F. Zheng, S. Zhao, J. Chen, and Z. Wang, "Repression of phosphoinositide-dependent protein kinase 1 expression by ciglitazone via Egr-1 represents a new approach for inhibition of lung cancer cell growth," Molecular Cancer, vol. 13, no. 1, p. 149, 2014, doi: 10.1186/1476-4598-13-149. S. P. Berasi et al., "Inhibition of Gluconeogenesis through Transcriptional Activation of EGR1 and DUSP4 by AMP-activated Kinase*," Journal of Biological Chemistry, vol. 281, no. 37, pp. 27167-27177, 2006, doi: 10.1074/jbc.M602416200. B. Chaube, P. Malvi, S. V. Singh, N. Mohammad, B. Viollet, and M. K. Bhat, "AMPK maintains energy homeostasis and survival in cancer cells via regulating p38/PGC-1α-mediated mitochondrial biogenesis," Cell Death Discovery, vol. 1, no. 1, p. 15063, 2015, doi: 10.1038/cddiscovery.2015.63. R. C. Rabinovitch et al., "AMPK Maintains Cellular Metabolic Homeostasis through Regulation of Mitochondrial Reactive Oxygen Species," Cell Reports, vol. 21, no. 1, pp. 1-9, 2017, doi: 10.1016/j.celrep.2017.09.026. D. Zhou, L. R. Palam, L. Jiang, J. Narasimhan, K. A. Staschke, and R. C. Wek, "Phosphorylation of eIF2 directs ATF5 translational control in response to diverse stress conditions," J Biol Chem, vol. 283, no. 11, pp. 7064-73, 2008, doi: 10.1074/jbc.M708530200. G. Li, W. Li, J. M. Angelastro, L. A. Greene, and D. X. Liu, "Identification of a Novel DNA Binding Site and a Transcriptional Target for Activating Transcription Factor 5 in C6 Glioma and MCF-7 Breast Cancer Cells," Molecular Cancer Research, vol. 7, no. 6, pp. 933-943, 2009, doi: 10.1158/1541-7786.Mcr-08-0365. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99678 | - |
| dc.description.abstract | 癌細胞的失控性增殖往往超越血管新生的速度。此特性導致實體腫瘤中心經常處於營養及氧氣供應不足的狀態，從而引起腫瘤內代謝壓力的形成。為了生存於如此惡劣的微環境，癌細胞需啟動壓力適應反應，其中可藉由轉錄因子實現。實驗室先前研究發現，在多種乳癌細胞株中，營養剝奪會顯著誘導壓力反應轉錄因子Early Growth Response 1 (EGR1)的表現，而在葡萄糖缺乏條件下，EGR1的表現會受到ROS/p38訊號途徑的調控。當EGR1的表現抑制非壓力狀態下乳癌細胞的生長，EGR1的表現卻促進葡萄糖缺乏下乳癌細胞的存活，顯示EGR1在乳癌中會依細胞所面臨的壓力而扮演雙重角色，且能協助這些細胞適應代謝壓力。然而，EGR1調控代謝壓力適應的具體分子機制及其功能意涵仍有待深入闡明。
代謝壓力適應反應不僅能幫助癌細胞維持生存，更能協助其獲得遠端轉移的能力。在轉移過程中，癌細胞會脫離原發腫瘤部位，而失去其與細胞外基質的接觸，進一步引發失巢凋亡。因此，癌細胞是否能抵抗失巢凋亡會顯著影響癌症轉移。本研究亦探討EGR1在乳癌細胞抵抗失巢凋亡當中潛在的角色。 西方墨點法分析顯示，乳癌細胞葡萄糖缺乏下誘導的EGR1蛋白會多出現一條約100 kDa的條帶，並經過體外去磷酸酶處理後確認此為磷酸化修飾。這表明在代謝壓力下，EGR1除了被誘導表現外，還會進行磷酸化修飾。為找尋代謝壓力乏下EGR1磷酸化位點，我們建立了EGR1磷酸化位點突變並發現T391A突變使得100 kDa的條帶在葡萄糖充足以及缺乏的情況下都幾乎消失。這些結果表明EGR1在T391位點會被磷酸化，且在蛋白表現量上升時更加顯著，包括代謝壓力的條件下。 EGR1 T391的磷酸化雖然不會改變蛋白質在細胞內座落的位置，但顯著影響其轉錄活性。透過藥物抑制劑及基因改造等方法，我們發現EGR1代謝壓力下的磷酸化受ROS和AMPK的調控。未來我們將進一步探討AMPK對EGR1 T391磷酸化的調控機制，以及這修飾對於乳癌細胞適應代謝壓力的影響。這些發現將有助於理解乳癌細胞適應代謝壓力的反應機制，為乳癌治療提供新的策略方向。 | zh_TW |
| dc.description.abstract | Solid tumors frequently experience intratumoral metabolic stress due to rapid cell growth that exceeds the vascular supply. To maintain cell survival under this stress, cancer cells must elicit stress-adaptive responses, which can be achieved by activating transcription factors. Our previous studies identified that the stress-responsive transcription factor Early Growth Response 1 (EGR1) is significantly induced in various breast cancer cell lines under various nutrient depletion conditions. Under glucose deprivation, this induction was regulated via the ROS/p38 pathway. While EGR1 expression inhibited cell proliferation in non-stressed cells, it promoted cell viability in glucose-deprived breast cancer cells, denoting the capability of EGR1 in mediating metabolic stress adaptation. However, its precise regulatory mechanisms and detailed functional impact in this context remain unclear.
In addition to supporting cell survival, metabolic stress adaptation in cancer cells may facilitate their metastatic escape. During metastasis, as cancer cells disseminate from the tumor mass, they become vulnerable to a programmed cell death triggered upon extracellular matrix detachment known as anoikis. Susceptibility toward anoikis highlights the importance of gaining anoikis resistance for cancer cells to metastasize. In this study, we delved into the possible contribution of EGR1 in the anoikis resistance of breast cancer cells. EGR1 was not only induced but also phosphorylated in breast cancer cells under glucose deprivation. This was evidenced by an additional EGR1 band migrating at 100 kDa in Western blot analysis, which ceased upon in vitro dephosphorylation. To locate the EGR1 phosphorylation site under metabolic stress, we employed site-directed mutagenesis. We identified that the additional EGR1 protein was nearly absent in the T391A mutant under both glucose-replenished and glucose-deprived conditions. This indicates that EGR1 is phosphorylated at T391, and this phosphorylation becomes evident as EGR1 expression increases under conditions such as metabolic stress. While EGR1 phosphorylation at T391 did not impact EGR1 nuclear localization, it was crucial for its transcriptional activity. Through pharmacological inhibition and genetic modification, we found that EGR1 phosphorylation under glucose deprivation was regulated by ROS and AMPK. However, further studies are required to elucidate the relation between AMPK and EGR1 T391 phosphorylation, as well as their detailed impact on breast cancer cells adapting to metabolic stress. Understanding how the cells respond to stress may provide a novel approach for breast cancer therapeutic intervention. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-09-17T16:21:04Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-09-17T16:21:04Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 誌謝 i
摘要 ii Abstract iv List of Abbreviations vi List of Figures xii List of Appendix xiv Chapter 1. Introduction 1 1.1 Breast cancer 1 1.1.1 Breast cancer subtypes, treatment plans, and prognosis 1 1.1.2 Breast cancer and metastasis 4 1.2 Intratumoral metabolic stress 5 1.3 Anoikis cell death 8 1.3.1 Anoikis resistance in cancer metastasis 9 1.3.2 Anoikis resistance under metabolic stress 11 1.4 Early growth response 1 (EGR1) 12 1.4.1 Early Growth Response (EGR) Family 12 1.4.2 Introduction to EGR1 13 1.4.3 EGR1 induction mechanisms 14 1.4.4 EGR1 in cancer 14 1.4.5 EGR1 in breast cancer 15 1.4.6 Post-translational modifications (PTMs) of EGR1 16 1.5 Metabolic stress-related protein kinases 19 1.5.1 Protein kinase CK2 19 1.5.2 p38 Mitogen-Activated Protein Kinase (MAPK) 21 1.5.3 General control non-depressible 2 (GCN2) 23 1.5.4 AMP-activated protein kinase (AMPK) 25 1.6 Previous studies on EGR1 from our laboratory 28 Chapter 2. Specific aim 30 Chapter 3. Materials and Methods 31 3.1 Cell culture 31 3.2 Cell transfection 32 3.3 RNA interference 32 3.3.1 siRNA knockdown 32 3.3.2 shRNA knockdown 33 3.4 Lentivirus production and transduction 33 3.5 Protein extraction and quantification 35 3.6 Western blotting 36 3.7 RNA extraction 37 3.8 Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) 38 3.9 Plasmid construction 39 3.9.1 pCMV-Tag2A-EGR1 mutants 39 3.9.2 N174-MCS-Flag-EGR1 mutants 40 3.10 Immunofluorescence 42 3.11 Dual-luciferase reporter assay 43 3.12 ACP cell viability assay 44 3.13 Anoikis assay 44 3.14 Statistical analysis 45 Chapter 4. Results 46 4.1 EGR1 was induced and phosphorylated in breast cancer cells under metabolic stress 46 4.2 Constructing EGR1 phosphorylation site mutants in breast cancer cell lines 46 4.3 The protein band migrating at 100 kDa was EGR1 phosphorylated at T391 47 4.4 Phosphorylation mutants of EGR1 did not affect its nuclear localization 48 4.5 EGR1 T391 phosphorylation was crucial for its transcriptional activity 49 4.6 The ability of EGR1 to promote cell viability under glucose deprivation may not be influenced by T391 phosphorylation 50 4.7 Investigating the role of EGR1 and its T391 phosphorylation in the anoikis resistance of breast cancer cells under metabolic stress 50 4.8 CK2 was unlikely to phosphorylate EGR1 under glucose deprivation 51 4.9 ROS regulated both EGR1 induction and phosphorylation under glucose deprivation 52 4.10 p38 was unlikely to phosphorylate EGR1 under glucose deprivation 53 4.11 GCN2 was unlikely to phosphorylate EGR1 under glucose deprivation 53 4.12 GCN2 regulated EGR1 transcription under glucose deprivation at the transcriptional level 54 4.13 AMPK may phosphorylate EGR1 under glucose deprivation 54 4.14 AMPK regulated EGR1 expression under glucose deprivation at the transcriptional level 55 Chapter 5. Discussion 57 Figure 69 Reference 86 Appendix 101 | - |
| dc.language.iso | en | - |
| dc.subject | 乳癌 | zh_TW |
| dc.subject | 代謝壓力 | zh_TW |
| dc.subject | 葡萄糖剝奪 | zh_TW |
| dc.subject | EGR1 | zh_TW |
| dc.subject | AMPK | zh_TW |
| dc.subject | 磷酸化 | zh_TW |
| dc.subject | glucose deprivation | en |
| dc.subject | breast cancer | en |
| dc.subject | phosphorylation | en |
| dc.subject | AMPK | en |
| dc.subject | EGR1 | en |
| dc.subject | metabolic stress | en |
| dc.title | 探討EGR1的磷酸化及其在乳癌細胞適應代謝壓力的功能 | zh_TW |
| dc.title | Unraveling Early Growth Response 1 (EGR1) Phosphorylation and Its Role in Breast Cancer Cells Adaptation to Metabolic Stress | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 楊雅倩;蘇剛毅;林亮音;卓爾婕 | zh_TW |
| dc.contributor.oralexamcommittee | Ya-Chien Yang;Kang-Yi Su;Liang-In Lin;Er-Chieh Cho | en |
| dc.subject.keyword | 乳癌,代謝壓力,葡萄糖剝奪,EGR1,AMPK,磷酸化, | zh_TW |
| dc.subject.keyword | breast cancer,metabolic stress,glucose deprivation,EGR1,AMPK,phosphorylation, | en |
| dc.relation.page | 103 | - |
| dc.identifier.doi | 10.6342/NTU202503267 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2025-08-07 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學系 | - |
| dc.date.embargo-lift | N/A | - |
| Appears in Collections: | 醫學檢驗暨生物技術學系 | |
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| ntu-113-2.pdf Restricted Access | 8.49 MB | Adobe PDF |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.