請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/102130完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 郭靜穎 | zh_TW |
| dc.contributor.advisor | Ching-Ying Kuo | en |
| dc.contributor.author | 鄭宇芯 | zh_TW |
| dc.contributor.author | Yu-Hsin Cheng | en |
| dc.date.accessioned | 2026-03-13T16:40:26Z | - |
| dc.date.available | 2026-03-14 | - |
| dc.date.copyright | 2026-03-13 | - |
| dc.date.issued | 2026 | - |
| dc.date.submitted | 2026-02-03 | - |
| dc.identifier.citation | 1. Kim, J., et al., Global patterns and trends in breast cancer incidence and mortality across 185 countries. Nat Med, 2025. 31(4): p. 1154-1162.
2. 衛生福利部-113年國人死因統計結果分析. 2025. 3. 中華民國112年癌症登記報告 2025. 4. Carvalho, E., et al., Molecular Subtypes and Mechanisms of Breast Cancer: Precision Medicine Approaches for Targeted Therapies. Cancers (Basel), 2025. 17(7). 5. Perou, C.M., et al., Molecular portraits of human breast tumours. Nature, 2000. 406(6797): p. 747-52. 6. Yu, N.Y., et al., Assessment of Long-term Distant Recurrence-Free Survival Associated With Tamoxifen Therapy in Postmenopausal Patients With Luminal A or Luminal B Breast Cancer. JAMA Oncol, 2019. 5(9): p. 1304-1309. 7. Brueggemeier, R.W., J.C. Hackett, and E.S. Diaz-Cruz, Aromatase inhibitors in the treatment of breast cancer. Endocr Rev, 2005. 26(3): p. 331-45. 8. Wang, X., et al., Recent progress of CDK4/6 inhibitors' current practice in breast cancer. Cancer Gene Ther, 2024. 31(9): p. 1283-1291. 9. Piccart-Gebhart, M.J., et al., Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med, 2005. 353(16): p. 1659-72. 10. Capelan, M., et al., Pertuzumab: new hope for patients with HER2-positive breast cancer. Ann Oncol, 2013. 24(2): p. 273-282. 11. Schlam, I. and S.M. Swain, HER2-positive breast cancer and tyrosine kinase inhibitors: the time is now. NPJ Breast Cancer, 2021. 7(1): p. 56. 12. Zimmerman, B.S. and F.J. Esteva, Next-Generation HER2-Targeted Antibody-Drug Conjugates in Breast Cancer. Cancers (Basel), 2024. 16(4). 13. Boyraz, B., et al., Trastuzumab emtansine (T-DM1) for HER2-positive breast cancer. Curr Med Res Opin, 2013. 29(4): p. 405-14. 14. Petit, T., et al., Trastuzumab deruxtecan in previously treated HER2-positive metastatic or unresectable breast cancer: Real-life data from the temporary use authorization program in France. Cancer Med, 2024. 13(9): p. e7168. 15. Derakhshan, F. and J.S. Reis-Filho, Pathogenesis of Triple-Negative Breast Cancer. Annu Rev Pathol, 2022. 17: p. 181-204. 16. Cortesi, L., H.S. Rugo, and C. Jackisch, An Overview of PARP Inhibitors for the Treatment of Breast Cancer. Target Oncol, 2021. 16(3): p. 255-282. 17. Barchiesi, G., et al., Emerging Role of PARP Inhibitors in Metastatic Triple Negative Breast Cancer. Current Scenario and Future Perspectives. Front Oncol, 2021. 11: p. 769280. 18. Thomas, R., G. Al-Khadairi, and J. Decock, Immune Checkpoint Inhibitors in Triple Negative Breast Cancer Treatment: Promising Future Prospects. Front Oncol, 2020. 10: p. 600573. 19. Nagayama, A., et al., Novel antibody-drug conjugates for triple negative breast cancer. Ther Adv Med Oncol, 2020. 12: p. 1758835920915980. 20. Chen, W., et al., Organotropism: new insights into molecular mechanisms of breast cancer metastasis. NPJ Precis Oncol, 2018. 2(1): p. 4. 21. Park, M., et al., Breast Cancer Metastasis: Mechanisms and Therapeutic Implications. Int J Mol Sci, 2022. 23(12). 22. Dai, Y., et al., Anoikis resistance--protagonists of breast cancer cells survive and metastasize after ECM detachment. Cell Commun Signal, 2023. 21(1): p. 190. 23. Shaw, P., et al., Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding. Cancer Lett, 2025. 624: p. 217750. 24. Riggio, A.I., K.E. Varley, and A.L. Welm, The lingering mysteries of metastatic recurrence in breast cancer. Br J Cancer, 2021. 124(1): p. 13-26. 25. Xia, Y., et al., Hypoxia-responsive nanomaterials for tumor imaging and therapy. Front Oncol, 2022. 12: p. 1089446. 26. Martinez-Reyes, I. and N.S. Chandel, Cancer metabolism: looking forward. Nat Rev Cancer, 2021. 21(10): p. 669-680. 27. Rodriguez-Enriquez, S., et al., Canonical and new generation anticancer drugs also target energy metabolism. Arch Toxicol, 2014. 88(7): p. 1327-50. 28. Cunha, A., et al., Targeting Glucose Metabolism in Cancer Cells as an Approach to Overcoming Drug Resistance. Pharmaceutics, 2023. 15(11). 29. Lines, C.L., et al., The integrated stress response in cancer progression: a force for plasticity and resistance. Front Oncol, 2023. 13: p. 1206561. 30. English, A.R. and G.K. Voeltz, Endoplasmic reticulum structure and interconnections with other organelles. Cold Spring Harb Perspect Biol, 2013. 5(4): p. a013227. 31. Bruce Alberts, A.J., Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter, Molecular Biology of the Cell: The Endoplasmic Reticulum. 4 ed. 2002. 32. Barazzuol, L., F. Giamogante, and T. Cali, Mitochondria Associated Membranes (MAMs): Architecture and physiopathological role. Cell Calcium, 2021. 94: p. 102343. 33. Chen, X. and J.R. Cubillos-Ruiz, Endoplasmic reticulum stress signals in the tumour and its microenvironment. Nat Rev Cancer, 2021. 21(2): p. 71-88. 34. Chen, X., et al., Endoplasmic reticulum stress: molecular mechanism and therapeutic targets. Signal Transduct Target Ther, 2023. 8(1): p. 352. 35. Hetz, C., The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol, 2012. 13(2): p. 89-102. 36. Jiang, D., M. Niwa, and A.C. Koong, Targeting the IRE1alpha-XBP1 branch of the unfolded protein response in human diseases. Semin Cancer Biol, 2015. 33: p. 48-56. 37. Rozpedek, W., et al., The Role of the PERK/eIF2alpha/ATF4/CHOP Signaling Pathway in Tumor Progression During Endoplasmic Reticulum Stress. Curr Mol Med, 2016. 16(6): p. 533-44. 38. Lei, Y., et al., Molecular mechanism of ATF6 in unfolded protein response and its role in disease. Heliyon, 2024. 10(5): p. e25937. 39. He, J., Y. Zhou, and L. Sun, Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy. Cell Commun Signal, 2024. 22(1): p. 89. 40. Madden, E., et al., The role of the unfolded protein response in cancer progression: From oncogenesis to chemoresistance. Biol Cell, 2019. 111(1): p. 1-17. 41. Krshnan, L., M.L. van de Weijer, and P. Carvalho, Endoplasmic Reticulum-Associated Protein Degradation. Cold Spring Harb Perspect Biol, 2022. 14(12). 42. Vembar, S.S. and J.L. Brodsky, One step at a time: endoplasmic reticulum-associated degradation. Nat Rev Mol Cell Biol, 2008. 9(12): p. 944-57. 43. Avivar-Valderas, A., et al., PERK integrates autophagy and oxidative stress responses to promote survival during extracellular matrix detachment. Mol Cell Biol, 2011. 31(17): p. 3616-29. 44. Lhomond, S., et al., Dual IRE1 RNase functions dictate glioblastoma development. EMBO Mol Med, 2018. 10(3). 45. Brewer, J.W. and J.A. Diehl, PERK mediates cell-cycle exit during the mammalian unfolded protein response. Proc Natl Acad Sci U S A, 2000. 97(23): p. 12625-30. 46. Conroy, L.R., et al., Emerging roles of N-linked glycosylation in brain physiology and disorders. Trends Endocrinol Metab, 2021. 32(12): p. 980-993. 47. Palorini, R., et al., Glucose starvation induces cell death in K-ras-transformed cells by interfering with the hexosamine biosynthesis pathway and activating the unfolded protein response. Cell Death Dis, 2013. 4(7): p. e732. 48. Cui, Y., et al., The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade. Front Cell Dev Biol, 2023. 11: p. 1275543. 49. Verfaillie, T., et al., Linking ER Stress to Autophagy: Potential Implications for Cancer Therapy. Int J Cell Biol, 2010. 2010: p. 930509. 50. Hetz, C. and F.R. Papa, The Unfolded Protein Response and Cell Fate Control. Mol Cell, 2018. 69(2): p. 169-181. 51. B'Chir, W., et al., The eIF2alpha/ATF4 pathway is essential for stress-induced autophagy gene expression. Nucleic Acids Res, 2013. 41(16): p. 7683-99. 52. Das, E., K.K. Sahu, and I. Roy, The functional role of Ire1 in regulating autophagy and proteasomal degradation under prolonged proteotoxic stress. FEBS J, 2023. 290(12): p. 3270-3289. 53. Ogata, M., et al., Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol, 2006. 26(24): p. 9220-31. 54. Meng, M., et al., A high-concentrate diet induces inflammatory injury via regulating Ca(2+)/CaMKKbeta-mediated autophagy in mammary gland tissue of dairy cows. Front Immunol, 2023. 14: p. 1186170. 55. Cui, T., et al., Molybdenum and cadmium co-exposure induces CaMKKbeta/AMPK/mTOR pathway mediated-autophagy by subcellular calcium redistribution in duck renal tubular epithelial cells. J Inorg Biochem, 2022. 236: p. 111974. 56. Khaminets, A., et al., Regulation of endoplasmic reticulum turnover by selective autophagy. Nature, 2015. 522(7556): p. 354-8. 57. Grumati, P., et al., Correction: Full length RTN3 regulates turnover of tubular endoplasmic reticulum via selective autophagy. Elife, 2025. 14. 58. Grumati, P., et al., Full length RTN3 regulates turnover of tubular endoplasmic reticulum via selective autophagy. Elife, 2017. 6. 59. Smith, M.D., et al., CCPG1 Is a Non-canonical Autophagy Cargo Receptor Essential for ER-Phagy and Pancreatic ER Proteostasis. Dev Cell, 2018. 44(2): p. 217-232 e11. 60. Vargas, G., et al., Negative Modulation of Macroautophagy by Stabilized HERPUD1 is Counteracted by an Increased ER-Lysosomal Network With Impact in Drug-Induced Stress Cell Survival. Front Cell Dev Biol, 2022. 10: p. 743287. 61. Iso, T., et al., HERP, a new primary target of Notch regulated by ligand binding. Mol Cell Biol, 2001. 21(17): p. 6071-9. 62. Shi, Q., et al., Notch signaling pathway in cancer: from mechanistic insights to targeted therapies. Signal Transduct Target Ther, 2024. 9(1): p. 128. 63. Sai, X., et al., Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein. J Biol Chem, 2002. 277(15): p. 12915-20. 64. NCBI Gene: HERPUD1 Gene – Homology. Available from: https://www.ncbi.nlm.nih.gov/gene/9709/ortholog/?scope=7776. 65. Kokame, K., et al., Herp, a new ubiquitin-like membrane protein induced by endoplasmic reticulum stress. J Biol Chem, 2000. 275(42): p. 32846-53. 66. van Laar, T., et al., The novel MMS-inducible gene Mif1/KIAA0025 is a target of the unfolded protein response pathway. FEBS Lett, 2000. 469(1): p. 123-31. 67. Leitman, J., et al., Herp coordinates compartmentalization and recruitment of HRD1 and misfolded proteins for ERAD. Molecular Biology of the Cell, 2014. 25(7): p. 1050-1060. 68. Paredes, F., et al., HERPUD1 governs tumor cell mitochondrial function via inositol 1,4,5-trisphosphate receptor-mediated calcium signaling. Free Radic Biol Med, 2024. 211: p. 24-34. 69. Torrealba, N., et al., Herpud1 negatively regulates pathological cardiac hypertrophy by inducing IP3 receptor degradation. Sci Rep, 2017. 7(1): p. 13402. 70. Ho, D.V. and J.Y. Chan, Induction of Herpud1 expression by ER stress is regulated by Nrf1. FEBS Lett, 2015. 589(5): p. 615-20. 71. Shaban, M.S., et al., Thapsigargin: key to new host-directed coronavirus antivirals? Trends in Pharmacological Sciences, 2022. 43(7): p. 557-568. 72. Kokame, K., H. Kato, and T. Miyata, Identification of ERSE-II, a new cis-acting element responsible for the ATF6-dependent mammalian unfolded protein response. J Biol Chem, 2001. 276(12): p. 9199-205. 73. Le, T.M., et al., Deletion of Herpud1 Enhances Heme Oxygenase-1 Expression in a Mouse Model of Parkinson's Disease. Parkinsons Dis, 2016. 2016: p. 6163934. 74. Liu, C., et al., Circ_002664/miR-182-5p/Herpud1 pathway importantly contributes to OGD/R-induced neuronal cell apoptosis. Mol Cell Probes, 2020. 53: p. 101585. 75. Lu, S., et al., Effects of Herpud1 in Methamphetamine-induced Neuronal Apoptosis. Curr Med Chem, 2025. 32(7): p. 1406-1422. 76. Paredes, F., et al., HERPUD1 protects against oxidative stress-induced apoptosis through downregulation of the inositol 1,4,5-trisphosphate receptor. Free Radic Biol Med, 2016. 90: p. 206-18. 77. Nie, X., et al., HERPUD1 promotes ovarian cancer cell survival by sustaining autophagy and inhibit apoptosis via PI3K/AKT/mTOR and p38 MAPK signaling pathways. BMC Cancer, 2022. 22(1): p. 1338. 78. Xiao, D.Z., Xingruo & He, Hengjing & Jamal, Muhammad & Zhang, Chengjie & Zhang, Xiaoyu & Xie, Songping & Zhang, Qiuping., HERPUD1 as a potential prognostic biomarker in lung cancer and association with migration and invasion. 2023. 79. Erzurumlu, Y., et al., HERPUD1, a Member of the Endoplasmic Reticulum Protein Quality Control Mechanism, may be a Good Target for Suppressing Tumorigenesis in Breast Cancer Cells. Turk J Pharm Sci, 2023. 20(3): p. 157-164. 80. Peng, Y., et al., Corosolic acid sensitizes ferroptosis by upregulating HERPUD1 in liver cancer cells. Cell Death Discov, 2022. 8(1): p. 376. 81. Quiroga, C., et al., Herp depletion protects from protein aggregation by up-regulating autophagy. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2013. 1833(12): p. 3295-3305. 82. Li, R., et al., Glucose Starvation-Caused Oxidative Stress Induces Inflammation and Autophagy in Human Gingival Fibroblasts. Antioxidants (Basel), 2022. 11(10). 83. Ricciardiello, F., et al., Inhibition of the Hexosamine Biosynthetic Pathway by targeting PGM3 causes breast cancer growth arrest and apoptosis. Cell Death Dis, 2018. 9(3): p. 377. 84. Yorimitsu, T. and D.J. Klionsky, Autophagy: molecular machinery for self-eating. Cell Death Differ, 2005. 12 Suppl 2(Suppl 2): p. 1542-52. 85. Mizushima, N. and M. Komatsu, Autophagy: renovation of cells and tissues. Cell, 2011. 147(4): p. 728-41. 86. Dawes, S., et al., Chaperone BiP controls ER stress sensor Ire1 through interactions with its oligomers. Life Sci Alliance, 2024. 7(10). 87. Jeon, Y.J. and Z.A. Ronai, The role of ER-associated degradation and ER-phagy in health and disease. Signal Transduct Target Ther, 2026. 11(1): p. 7. 88. Huang, C.H., et al., Role of HERP and a HERP-related protein in HRD1-dependent protein degradation at the endoplasmic reticulum. J Biol Chem, 2014. 289(7): p. 4444-54. 89. Schulz, J., et al., Conserved cytoplasmic domains promote Hrd1 ubiquitin ligase complex formation for ER-associated degradation (ERAD). J Cell Sci, 2017. 130(19): p. 3322-3335. 90. Wang, H.H., et al., SEL1L-HRD1-mediated ERAD in mammals. Nat Cell Biol, 2025. 27(7): p. 1063-1073. 91. Fusakio, M.E., et al., Transcription factor ATF4 directs basal and stress-induced gene expression in the unfolded protein response and cholesterol metabolism in the liver. Mol Biol Cell, 2016. 27(9): p. 1536-51. 92. Everson, W.V., et al., Effect of amino acid deprivation on initiation of protein synthesis in rat hepatocytes. Am J Physiol, 1989. 256(1 Pt 1): p. C18-27. 93. Jousse, C., et al., Amino acid limitation regulates CHOP expression through a specific pathway independent of the unfolded protein response. FEBS Letters, 1999. 448(2-3): p. 211-216. 94. Hao, C., et al., Effect of glycosylation on protein folding: From biological roles to chemical protein synthesis. iScience, 2025. 28(6): p. 112605. 95. Kuzu, O.F., L.J.T. Granerud, and F. Saatcioglu, Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations. Signal Transduct Target Ther, 2025. 10(1): p. 358. 96. Liu, S., et al., Autophagy: Regulator of cell death. Cell Death Dis, 2023. 14(10): p. 648. 97. Senft, D. and Z.A. Ronai, UPR, autophagy, and mitochondria crosstalk underlies the ER stress response. Trends Biochem Sci, 2015. 40(3): p. 141-8. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/102130 | - |
| dc.description.abstract | 實質固態腫瘤因快速增殖導致血管新生不足，造成氧氣與營養供應不穩，加上代謝廢物堆積，使腫瘤細胞長期處於缺氧與營養缺乏的代謝壓力微環境。代謝壓力會造成癌細胞生長停滯，甚至導致腫瘤中心區域出現壞死，為了適應這種不利的環境，癌細胞會啟動多種壓力反應機制，以維持癌細胞的功能穩定與存活，甚至進一步強化侵襲與轉移能力。然而在代謝壓力下，癌細胞如何調節對代謝壓力的適應並生存，其調控機制仍待完整釐清。
本研究透過分析三陰性乳癌(triple negative breast cancer, TNBC)細胞 MDA-MB-231在葡萄糖剝奪下的基因微陣列(microarray)資料發現，受誘導的上調基因高度富集於內質網壓力與未折疊蛋白反應路徑。在眾多差異表現基因中發現，HERPUD1為上調幅度最顯著且對葡萄糖缺乏高度敏感。此外，利用乳癌公開資料庫進行基因富集(Gene Set Enrichment Analysis, GSEA)分析顯示，HERPUD1的表現與未折疊蛋白反應、蛋白質分泌等路徑呈正相關。HERPUD1為一內質網壓力誘導蛋白，參與內質網相關蛋白降解(ERAD)與蛋白品質控制，其表現常受到未折疊蛋白反應(unfolded protein response, UPR)調控，並與細胞對壓力的適應機制密切相關。 經由細胞實驗發現，HERPUD1主要在三陰性乳癌中被誘導，且其蛋白質表現僅在葡萄糖缺乏時明顯上升；機制層面上，我們發現葡萄糖缺乏所誘導的 HERPUD1上調不依賴ROS/p38訊號，且主要透過未折疊蛋白反應中的IRE1⍺分支調控。在功能上，HERPUD1敲低會使三陰性乳癌細胞於葡萄糖缺乏下的未折疊蛋白反應訊號顯著增強與延長，且自噬通量顯著提高，顯示在HERPUD1缺失的情況下，細胞可能透過代償性自噬協助清除異常蛋白以維持蛋白質恆定(proteostasis)來維持細胞存活與增殖。 綜合上述，我們發現HERPUD1是三陰性乳癌細胞應對代謝壓力的關鍵調節蛋白，在葡萄糖缺乏下透過IRE1⍺分支被誘導表現，並藉由調控內質網壓力強度與抑制過度自噬，在細胞壓力適應與生長控制間取得平衡。 | zh_TW |
| dc.description.abstract | Solid tumors often grow in metabolically stressed microenvironments due to their rapid proliferation, which leads to insufficient and abnormal angiogenesis. As a result, tumor cells experience hypoxia, nutrient deprivation, and accumulation of acidic waste products. These conditions inhibit tumor growth and may cause central necrosis. To survive, cancer cells adapt through metabolic reprogramming and activation of stress response pathways, but the mechanisms underlying such as adaptations remain incompletely understood.
Through analysis of in-house microarray data from the triple-negative breast cancer (TNBC) cell line MDA-MB-231 under glucose deprivation, HERPUD1 was identified as a highly sensitive candidate gene significantly enriched in endoplasmic reticulum (ER) stress and unfolded protein response (UPR) pathways. This induction was specific to the triple-negative breast cancer (TNBC) subtype and glucose levels, with no comparable protein-level response to glutamine or arginine withdrawal. Mechanistically, glucose deprivation induced HERPUD1 expression was independent of ROS/p38 signaling but was regulated via the IRE1⍺ signaling axis. Knockdown of HERPUD1 in TNBC cells exacerbated UPR signaling under glucose deprivation. And further investigation revealed that the loss of HERPUD1 significantly accelerated autophagic flux, supported by LC3 conversion and LC3 dynamics. This compensatory autophagy may facilitate the clearance of abnormal proteins to maintain proteostasis. Furthermore, absence of HERPUD1 conferred a survival advantage and enhanced colony-formation ability under low-glucose conditions, suggesting that HERPUD1 constrained the survival and clonogenic growth of TNBC cells under glucose deprivation. This benefit was autophagy-dependent as it could be abolished by inhibiting autophagic flux. In conclusion, HERPUD1 is a critical regulator that balances stress adaptation and growth control by modulating ER stress intensity and suppressing excessive autophagy via the IRE1⍺ axis. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2026-03-13T16:40:26Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2026-03-13T16:40:26Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員審定書 i
誌謝 ii 中文摘要 iii Abstract iv 縮寫表 vi 圖次 xii 第一章 前言 1 1.1 乳癌 1 1.1.1 乳癌的分類與治療 1 1.2 腫瘤內代謝壓力 5 1.3 內質網的構造與功能 7 1.4 內質網壓力反應 9 1.4.1 未折疊蛋白反應 (Unfolded Protein Response, UPR) 9 1.4.2 內質網相關蛋白質降解機制(Endoplasmic reticulum-associated protein degradation, ERAD) 11 1.4.3 腫瘤內的內質網壓力 12 1.4.4 代謝壓力與內質網壓力的關係 13 1.4.5 內質網壓力與細胞自噬於蛋白質品質管控中扮演的角色 14 1.5 同型半胱氨酸反應性內質網駐留泛素樣結構域家族 (Homocysteine-responsive Endoplasmic Reticulum-resident Ubiquitin-like Domain family) 15 1.6 Homocysteine-responsive Endoplasmic Reticulum-resident Ubiquitin-like Domain member 1 (HERPUD1) 16 1.6.1 HERPUD1的誘導機制 17 1.6.2 HERPUD1與疾病 17 1.6.3 HERPUD1與癌症 18 1.6.4 HERPUD1與細胞自噬 19 第二章 研究目的 21 第三章 研究方法 22 3.1 細胞培養與試劑 22 3.2 慢病毒製作、轉導與細胞篩選 23 3.2.1 shRNA轉染試驗 23 3.2.2 siRNA轉染試驗 24 3.3 RNA萃取、定量與反轉錄 24 3.4 即時定量聚合酶連鎖反應(Real-time PCR, qPCR) 24 3.5 蛋白質萃取與定量 25 3.6 蛋白質電泳與西方墨點法 25 3.8 細胞群落形成試驗 27 3.9質體建構及製備：N174-HERP1-Myc-Flag 27 3.10 免疫螢光染色 28 3.11 微陣列資料差異基因篩選與DAVID路徑富集分析 29 3.12 基因富集分析(GSEA) 30 3.13 統計分析 30 第四章 結果 31 4.1葡萄糖缺乏誘發三陰性乳癌細胞株內質網壓力與未折疊蛋白反應 31 4.2 葡萄糖缺乏顯著誘導三陰性乳癌細胞株中HERPUD1的表現 31 4.3 HERPUD1僅於葡萄糖缺乏時被誘導且分佈於內質網 33 4.4 葡萄糖缺乏造成的HERPUD1上調可能與ROS/p38訊號無關 33 4.5 葡萄糖缺乏引發內質網壓力，進而誘導HERPUD1上調 34 4.6 HERPUD1 參與代謝壓力下的內質網壓力調控作用 34 4.7 HERPUD1敲低促進細胞於代謝壓力下的自噬作用 35 4.8 HERPUD1可能透過抑制ITPR3–CaMKKβ–AMPK訊號軸，抑制葡萄糖缺乏誘發的自噬反應 38 4.9 HERPUD1在養分充足的情況下不影響乳癌細胞的存活與增殖 38 4.10 HERPUD1在代謝壓力下抑制乳癌細胞存活與增殖 38 4.11 建立穩定過表現與再表現HERPUD1細胞株 39 4.12 HERPUD1於葡萄糖缺乏下的誘導可能由IRE1⍺調控 40 第五章 結論及討論 42 圖 49 參考資料 76 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 乳癌 | - |
| dc.subject | 代謝壓力 | - |
| dc.subject | HERPUD1 | - |
| dc.subject | 內質網壓力 | - |
| dc.subject | 未折疊蛋白反應 | - |
| dc.subject | 自噬作用 | - |
| dc.subject | breast cancer | - |
| dc.subject | metabolic stress | - |
| dc.subject | HERPUD1 | - |
| dc.subject | endoplasmic reticulum stress | - |
| dc.subject | unfolded protein response | - |
| dc.subject | autophagy | - |
| dc.title | 探討內質網壓力誘導蛋白 HERPUD1 在乳癌細胞 代謝壓力反應中的功能 | zh_TW |
| dc.title | Investigating the Role of the Endoplasmic Reticulum Stress-inducible Protein HERPUD1 in Metabolic Stress Response of Breast Cancer Cells | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 114-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 蘇剛毅;楊雅倩;林能裕;卓爾婕 | zh_TW |
| dc.contributor.oralexamcommittee | Kang-Yi Su;Ya-Chien Yang;Neng-Yu Lin;Er-Chieh Cho | en |
| dc.subject.keyword | 乳癌,代謝壓力HERPUD1內質網壓力未折疊蛋白反應自噬作用 | zh_TW |
| dc.subject.keyword | breast cancer,metabolic stressHERPUD1endoplasmic reticulum stressunfolded protein responseautophagy | en |
| dc.relation.page | 85 | - |
| dc.identifier.doi | 10.6342/NTU202600638 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2026-02-04 | - |
| 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 | - |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-114-1.pdf 未授權公開取用 | 7.2 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。