請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78063完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 余佳慧(LINDA CHIA-HUI YU) | |
| dc.contributor.author | YEN-JU HUANG | en |
| dc.contributor.author | 黃彥儒 | zh_TW |
| dc.date.accessioned | 2021-07-11T14:41:06Z | - |
| dc.date.available | 2025-08-17 | |
| dc.date.copyright | 2020-09-10 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-17 | |
| dc.identifier.citation | 1. Greenwood-Van Meerveld B, Johnson AC, Grundy D. Gastrointestinal Physiology and Function. Handb Exp Pharmacol 2017;239:1-16. 2. Potten CS, Booth C, Pritchard DM. The intestinal epithelial stem cell: the mucosal governor. Int J Exp Pathol 1997;78:219-43. 3. Darwich AS, Aslam U, Ashcroft DM, et al. Meta-analysis of the turnover of intestinal epithelia in preclinical animal species and humans. Drug Metab Dispos 2014;42:2016-22. 4. Gehart H, Clevers H. Tales from the crypt: new insights into intestinal stem cells. Nat Rev Gastroenterol Hepatol 2019;16:19-34. 5. Cheng H, Leblond CP. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian Theory of the origin of the four epithelial cell types. Am J Anat 1974;141:537-61. 6. Clevers H. The intestinal crypt, a prototype stem cell compartment. Cell 2013;154:274-84. 7. Barker N, van de Wetering M, Clevers H. The intestinal stem cell. Genes Dev 2008;22:1856-64. 8. Umar S. Intestinal stem cells. Curr Gastroenterol Rep 2010;12:340-8. 9. Potten CS, Kovacs L, Hamilton E. Continuous labelling studies on mouse skin and intestine. Cell Tissue Kinet 1974;7:271-83. 10. Potten CS. Extreme sensitivity of some intestinal crypt cells to X and gamma irradiation. Nature 1977;269:518-21. 11. Potten CS, Owen G, Booth D. Intestinal stem cells protect their genome by selective segregation of template DNA strands. J Cell Sci 2002;115:2381-8. 12. Sangiorgi E, Capecchi MR. Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet 2008;40:915-20. 13. Breault DT, Min IM, Carlone DL, et al. Generation of mTert-GFP mice as a model to identify and study tissue progenitor cells. Proc Natl Acad Sci U S A 2008;105:10420-5. 14. Takeda N, Jain R, LeBoeuf MR, et al. Interconversion between intestinal stem cell populations in distinct niches. Science 2011;334:1420-4. 15. Powell AE, Wang Y, Li Y, et al. The pan-ErbB negative regulator Lrig1 is an intestinal stem cell marker that functions as a tumor suppressor. Cell 2012;149:146-58. 16. May R, Riehl TE, Hunt C, et al. Identification of a novel putative gastrointestinal stem cell and adenoma stem cell marker, doublecortin and CaM kinase-like-1, following radiation injury and in adenomatous polyposis coli/multiple intestinal neoplasia mice. Stem Cells 2008;26:630-7. 17. Munoz J, Stange DE, Schepers AG, et al. The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent '+4' cell markers. EMBO J 2012;31:3079-91. 18. Barker N, van Oudenaarden A, Clevers H. Identifying the stem cell of the intestinal crypt: strategies and pitfalls. Cell Stem Cell 2012;11:452-60. 19. Cheng H, Leblond CP. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. I. Columnar cell. Am J Anat 1974;141:461-79. 20. Barker N, van Es JH, Kuipers J, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 2007;449:1003-7. 21. Schuijers J, Junker JP, Mokry M, et al. Ascl2 acts as an R-spondin/Wnt-responsive switch to control stemness in intestinal crypts. Cell Stem Cell 2015;16:158-70. 22. Kayahara T, Sawada M, Takaishi S, et al. Candidate markers for stem and early progenitor cells, Musashi-1 and Hes1, are expressed in crypt base columnar cells of mouse small intestine. FEBS Lett 2003;535:131-5. 23. Potten CS, Booth C, Tudor GL, et al. Identification of a putative intestinal stem cell and early lineage marker; musashi-1. Differentiation 2003;71:28-41. 24. Maria Cambuli F, Rezza A, Nadjar J, et al. Brief report: musashi1-eGFP mice, a new tool for differential isolation of the intestinal stem cell populations. Stem Cells 2013;31:2273-8. 25. van der Flier LG, Haegebarth A, Stange DE, et al. OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells. Gastroenterology 2009;137:15-7. 26. Li L, Clevers H. Coexistence of quiescent and active adult stem cells in mammals. Science 2010;327:542-5. 27. Schuijers J, Clevers H. Adult mammalian stem cells: the role of Wnt, Lgr5 and R-spondins. EMBO J 2012;31:2685-96. 28. Sato T, van Es JH, Snippert HJ, et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 2011;469:415-8. 29. Farin HF, Van Es JH, Clevers H. Redundant sources of Wnt regulate intestinal stem cells and promote formation of Paneth cells. Gastroenterology 2012;143:1518-1529 e7. 30. Sato T, Clevers H. Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science 2013;340:1190-4. 31. Rothenberg ME, Nusse Y, Kalisky T, et al. Identification of a cKit(+) colonic crypt base secretory cell that supports Lgr5(+) stem cells in mice. Gastroenterology 2012;142:1195-1205 e6. 32. Sasaki N, Sachs N, Wiebrands K, et al. Reg4+ deep crypt secretory cells function as epithelial niche for Lgr5+ stem cells in colon. Proc Natl Acad Sci U S A 2016;113:E5399-407. 33. Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 1978;4:7-25. 34. Medema JP, Vermeulen L. Microenvironmental regulation of stem cells in intestinal homeostasis and cancer. Nature 2011;474:318-26. 35. Spit M, Koo BK, Maurice MM. Tales from the crypt: intestinal niche signals in tissue renewal, plasticity and cancer. Open Biol 2018;8. 36. Sato T, Vries RG, Snippert HJ, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 2009;459:262-5. 37. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 2004;20:781-810. 38. Fevr T, Robine S, Louvard D, et al. Wnt/beta-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells. Mol Cell Biol 2007;27:7551-9. 39. Nusse R, Clevers H. Wnt/beta-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. Cell 2017;169:985-999. 40. Haegebarth A, Clevers H. Wnt signaling, lgr5, and stem cells in the intestine and skin. Am J Pathol 2009;174:715-21. 41. Kim BM, Mao J, Taketo MM, et al. Phases of canonical Wnt signaling during the development of mouse intestinal epithelium. Gastroenterology 2007;133:529-38. 42. Hrckulak D, Janeckova L, Lanikova L, et al. Wnt Effector TCF4 Is Dispensable for Wnt Signaling in Human Cancer Cells. Genes (Basel) 2018;9. 43. Korinek V, Barker N, Moerer P, et al. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet 1998;19:379-83. 44. Pinto D, Gregorieff A, Begthel H, et al. Canonical Wnt signals are essential for homeostasis of the intestinal epithelium. Genes Dev 2003;17:1709-13. 45. Byun T, Karimi M, Marsh JL, et al. Expression of secreted Wnt antagonists in gastrointestinal tissues: potential role in stem cell homeostasis. J Clin Pathol 2005;58:515-9. 46. Kim KA, Kakitani M, Zhao J, et al. Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science 2005;309:1256-9. 47. Kuhnert F, Davis CR, Wang HT, et al. Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1. Proc Natl Acad Sci U S A 2004;101:266-71. 48. Farin HF, Jordens I, Mosa MH, et al. Visualization of a short-range Wnt gradient in the intestinal stem-cell niche. Nature 2016;530:340-3. 49. Durand A, Donahue B, Peignon G, et al. Functional intestinal stem cells after Paneth cell ablation induced by the loss of transcription factor Math1 (Atoh1). Proc Natl Acad Sci U S A 2012;109:8965-70. 50. Kim TH, Escudero S, Shivdasani RA. Intact function of Lgr5 receptor-expressing intestinal stem cells in the absence of Paneth cells. Proc Natl Acad Sci U S A 2012;109:3932-7. 51. Louvi A, Artavanis-Tsakonas S. Notch signalling in vertebrate neural development. Nat Rev Neurosci 2006;7:93-102. 52. Chiba S. Notch signaling in stem cell systems. Stem Cells 2006;24:2437-47. 53. Crosnier C, Stamataki D, Lewis J. Organizing cell renewal in the intestine: stem cells, signals and combinatorial control. Nat Rev Genet 2006;7:349-59. 54. Fortini ME. Gamma-secretase-mediated proteolysis in cell-surface-receptor signalling. Nat Rev Mol Cell Biol 2002;3:673-84. 55. Six E, Ndiaye D, Laabi Y, et al. The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and gamma-secretase. Proc Natl Acad Sci U S A 2003;100:7638-43. 56. Kao HY, Ordentlich P, Koyano-Nakagawa N, et al. A histone deacetylase corepressor complex regulates the Notch signal transduction pathway. Genes Dev 1998;12:2269-77. 57. Lai EC. Keeping a good pathway down: transcriptional repression of Notch pathway target genes by CSL proteins. EMBO Rep 2002;3:840-5. 58. Fryer CJ, Lamar E, Turbachova I, et al. Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex. Genes Dev 2002;16:1397-411. 59. van Es JH, Sato T, van de Wetering M, et al. Dll1+ secretory progenitor cells revert to stem cells upon crypt damage. Nat Cell Biol 2012;14:1099-1104. 60. Fre S, Huyghe M, Mourikis P, et al. Notch signals control the fate of immature progenitor cells in the intestine. Nature 2005;435:964-8. 61. Abud HE, Watson N, Heath JK. Growth of intestinal epithelium in organ culture is dependent on EGF signalling. Exp Cell Res 2005;303:252-62. 62. Marquardt H, Hunkapiller MW, Hood LE, et al. Rat transforming growth factor type 1: structure and relation to epidermal growth factor. Science 1984;223:1079-82. 63. Suzuki A, Sekiya S, Gunshima E, et al. EGF signaling activates proliferation and blocks apoptosis of mouse and human intestinal stem/progenitor cells in long-term monolayer cell culture. Lab Invest 2010;90:1425-36. 64. Xu N, Wang SQ, Tan D, et al. EGFR, Wingless and JAK/STAT signaling cooperatively maintain Drosophila intestinal stem cells. Dev Biol 2011;354:31-43. 65. Jiang H, Edgar BA. EGFR signaling regulates the proliferation of Drosophila adult midgut progenitors. Development 2009;136:483-93. 66. Basak O, Beumer J, Wiebrands K, et al. Induced Quiescence of Lgr5+ Stem Cells in Intestinal Organoids Enables Differentiation of Hormone-Producing Enteroendocrine Cells. Cell Stem Cell 2017;20:177-190 e4. 67. Hardwick JC, Van Den Brink GR, Bleuming SA, et al. Bone morphogenetic protein 2 is expressed by, and acts upon, mature epithelial cells in the colon. Gastroenterology 2004;126:111-21. 68. Massague J. TGFbeta signalling in context. Nat Rev Mol Cell Biol 2012;13:616-30. 69. Hardwick JC, Kodach LL, Offerhaus GJ, et al. Bone morphogenetic protein signalling in colorectal cancer. Nat Rev Cancer 2008;8:806-12. 70. Haramis AP, Begthel H, van den Born M, et al. De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine. Science 2004;303:1684-6. 71. Qi Z, Li Y, Zhao B, et al. BMP restricts stemness of intestinal Lgr5(+) stem cells by directly suppressing their signature genes. Nat Commun 2017;8:13824. 72. He XC, Zhang J, Tong WG, et al. BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nat Genet 2004;36:1117-21. 73. Stzepourginski I, Nigro G, Jacob JM, et al. CD34+ mesenchymal cells are a major component of the intestinal stem cells niche at homeostasis and after injury. Proc Natl Acad Sci U S A 2017;114:E506-E513. 74. Kosinski C, Li VS, Chan AS, et al. Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. Proc Natl Acad Sci U S A 2007;104:15418-23. 75. Davis H, Irshad S, Bansal M, et al. Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche. Nat Med 2015;21:62-70. 76. Bijlsma MF, Spek CA, Peppelenbosch MP. Hedgehog: an unusual signal transducer. Bioessays 2004;26:387-94. 77. van Dop WA, Uhmann A, Wijgerde M, et al. Depletion of the colonic epithelial precursor cell compartment upon conditional activation of the hedgehog pathway. Gastroenterology 2009;136:2195-2203 e1-7. 78. Madison BB, Braunstein K, Kuizon E, et al. Epithelial hedgehog signals pattern the intestinal crypt-villus axis. Development 2005;132:279-89. 79. Wang LC, Nassir F, Liu ZY, et al. Disruption of hedgehog signaling reveals a novel role in intestinal morphogenesis and intestinal-specific lipid metabolism in mice. Gastroenterology 2002;122:469-82. 80. van den Brink GR, Bleuming SA, Hardwick JC, et al. Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation. Nat Genet 2004;36:277-82. 81. Zacharias WJ, Li X, Madison BB, et al. Hedgehog is an anti-inflammatory epithelial signal for the intestinal lamina propria. Gastroenterology 2010;138:2368-77, 2377 e1-4. 82. Varnat F, Zacchetti G, Ruiz i Altaba A. Hedgehog pathway activity is required for the lethality and intestinal phenotypes of mice with hyperactive Wnt signaling. Mech Dev 2010;127:73-81. 83. Li VS, Clevers H. Intestinal regeneration: YAP-tumor suppressor and oncoprotein? Curr Biol 2013;23:R110-2. 84. Meng Z, Moroishi T, Guan KL. Mechanisms of Hippo pathway regulation. Genes Dev 2016;30:1-17. 85. Gregorieff A, Wrana JL. Hippo signalling in intestinal regeneration and cancer. Curr Opin Cell Biol 2017;48:17-25. 86. Sebio A, Lenz HJ. Molecular Pathways: Hippo Signaling, a Critical Tumor Suppressor. Clin Cancer Res 2015;21:5002-7. 87. Cai J, Zhang N, Zheng Y, et al. The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program. Genes Dev 2010;24:2383-8. 88. Karpowicz P, Perez J, Perrimon N. The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development 2010;137:4135-45. 89. Zhou D, Zhang Y, Wu H, et al. Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. Proc Natl Acad Sci U S A 2011;108:E1312-20. 90. Imajo M, Ebisuya M, Nishida E. Dual role of YAP and TAZ in renewal of the intestinal epithelium. Nat Cell Biol 2015;17:7-19. 91. Azzolin L, Panciera T, Soligo S, et al. YAP/TAZ incorporation in the beta-catenin destruction complex orchestrates the Wnt response. Cell 2014;158:157-70. 92. Park HW, Kim YC, Yu B, et al. Alternative Wnt Signaling Activates YAP/TAZ. Cell 2015;162:780-94. 93. Gregorieff A, Liu Y, Inanlou MR, et al. Yap-dependent reprogramming of Lgr5(+) stem cells drives intestinal regeneration and cancer. Nature 2015;526:715-8. 94. Potier MC, Chelot E, Pekarsky Y, et al. The human myosin light chain kinase (MLCK) from hippocampus: cloning, sequencing, expression, and localization to 3qcen-q21. Genomics 1995;29:562-70. 95. Manning G, Whyte DB, Martinez R, et al. The protein kinase complement of the human genome. Science 2002;298:1912-34. 96. Garcia JG, Lazar V, Gilbert-McClain LI, et al. Myosin light chain kinase in endothelium: molecular cloning and regulation. Am J Respir Cell Mol Biol 1997;16:489-94. 97. Verin AD, Lazar V, Torry RJ, et al. Expression of a novel high molecular-weight myosin light chain kinase in endothelium. Am J Respir Cell Mol Biol 1998;19:758-66. 98. Herring BP, El-Mounayri O, Gallagher PJ, et al. Regulation of myosin light chain kinase and telokin expression in smooth muscle tissues. Am J Physiol Cell Physiol 2006;291:C817-27. 99. Gallagher PJ, Herring BP. The carboxyl terminus of the smooth muscle myosin light chain kinase is expressed as an independent protein, telokin. J Biol Chem 1991;266:23945-52. 100. Han YJ, Ma SF, Yourek G, et al. A transcribed pseudogene of MYLK promotes cell proliferation. FASEB J 2011;25:2305-12. 101. De Lanerolle P, Strauss JD, Felsen R, et al. Effects of antibodies to myosin light chain kinase on contractility and myosin phosphorylation in chemically permeabilized smooth muscle. Circ Res 1991;68:457-65. 102. Garcia JG, Davis HW, Patterson CE. Regulation of endothelial cell gap formation and barrier dysfunction: role of myosin light chain phosphorylation. J Cell Physiol 1995;163:510-22. 103. Gao Y, Ye LH, Kishi H, et al. Myosin light chain kinase as a multifunctional regulatory protein of smooth muscle contraction. IUBMB Life 2001;51:337-44. 104. Fishkind DJ, Cao LG, Wang YL. Microinjection of the catalytic fragment of myosin light chain kinase into dividing cells: effects on mitosis and cytokinesis. J Cell Biol 1991;114:967-75. 105. Dulyaninova NG, Patskovsky YV, Bresnick AR. The N-terminus of the long MLCK induces a disruption in normal spindle morphology and metaphase arrest. J Cell Sci 2004;117:1481-93. 106. Cunningham KE, Turner JR. Myosin light chain kinase: pulling the strings of epithelial tight junction function. Ann N Y Acad Sci 2012;1258:34-42. 107. Lazar V, Garcia JG. A single human myosin light chain kinase gene (MLCK; MYLK). Genomics 1999;57:256-67. 108. Brown M, Adyshev D, Bindokas V, et al. Quantitative distribution and colocalization of non-muscle myosin light chain kinase isoforms and cortactin in human lung endothelium. Microvasc Res 2010;80:75-88. 109. Clayburgh DR, Rosen S, Witkowski ED, et al. A differentiation-dependent splice variant of myosin light chain kinase, MLCK1, regulates epithelial tight junction permeability. J Biol Chem 2004;279:55506-13. 110. Zhou T, Wang T, Garcia JG. Genes influenced by the non-muscle isoform of Myosin light chain kinase impact human cancer prognosis. PLoS One 2014;9:e94325. 111. Lee WS, Seo G, Shin HJ, et al. Identification of differentially expressed genes in microsatellite stable HNPCC and sporadic colon cancer. J Surg Res 2008;144:29-35. 112. Curtis C, Shah SP, Chin SF, et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 2012;486:346-52. 113. Zhao H, Langerod A, Ji Y, et al. Different gene expression patterns in invasive lobular and ductal carcinomas of the breast. Mol Biol Cell 2004;15:2523-36. 114. Choi C, Helfman DM. The Ras-ERK pathway modulates cytoskeleton organization, cell motility and lung metastasis signature genes in MDA-MB-231 LM2. Oncogene 2014;33:3668-76. 115. Fujita A, Gomes LR, Sato JR, et al. Multivariate gene expression analysis reveals functional connectivity changes between normal/tumoral prostates. BMC Syst Biol 2008;2:106. 116. Leveille N, Fournier A, Labrie C. Androgens down-regulate myosin light chain kinase in human prostate cancer cells. J Steroid Biochem Mol Biol 2009;114:174-9. 117. Minamiya Y, Nakagawa T, Saito H, et al. Increased expression of myosin light chain kinase mRNA is related to metastasis in non-small cell lung cancer. Tumour Biol 2005;26:153-7. 118. Kim DY, Helfman DM. Loss of MLCK leads to disruption of cell-cell adhesion and invasive behavior of breast epithelial cells via increased expression of EGFR and ERK/JNK signaling. Oncogene 2016;35:4495-508. 119. Klemke RL, Cai S, Giannini AL, et al. Regulation of cell motility by mitogen-activated protein kinase. J Cell Biol 1997;137:481-92. 120. Zhang L, Huang D, Shao D, et al. Fenretinide inhibits the proliferation and migration of human liver cancer HepG2 cells by downregulating the activation of myosin light chain kinase through the p38MAPK signaling pathway. Oncol Rep 2018;40:518-526. 121. Nguyen DH, Catling AD, Webb DJ, et al. Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner. J Cell Biol 1999;146:149-64. 122. Zhou X, Liu Y, You J, et al. Myosin light-chain kinase contributes to the proliferation and migration of breast cancer cells through cross-talk with activated ERK1/2. Cancer Lett 2008;270:312-27. 123. Tohtong R, Phattarasakul K, Jiraviriyakul A, et al. Dependence of metastatic cancer cell invasion on MLCK-catalyzed phosphorylation of myosin regulatory light chain. Prostate Cancer Prostatic Dis 2003;6:212-6. 124. Mierke CT, Frey B, Fellner M, et al. Integrin alpha5beta1 facilitates cancer cell invasion through enhanced contractile forces. J Cell Sci 2011;124:369-83. 125. Gu LZ, Hu WY, Antic N, et al. Inhibiting myosin light chain kinase retards the growth of mammary and prostate cancer cells. Eur J Cancer 2006;42:948-57. 126. Cui WJ, Liu Y, Zhou XL, et al. Myosin light chain kinase is responsible for high proliferative ability of breast cancer cells via anti-apoptosis involving p38 pathway. Acta Pharmacol Sin 2010;31:725-32. 127. Fazal F, Gu L, Ihnatovych I, et al. Inhibiting myosin light chain kinase induces apoptosis in vitro and in vivo. Mol Cell Biol 2005;25:6259-66. 128. Suzuki M, Nagaishi T, Yamazaki M, et al. Myosin light chain kinase expression induced via tumor necrosis factor receptor 2 signaling in the epithelial cells regulates the development of colitis-associated carcinogenesis. PLoS One 2014;9:e88369. 129. Avizienyte E, Brunton VG, Fincham VJ, et al. The SRC-induced mesenchymal state in late-stage colon cancer cells. Cells Tissues Organs 2005;179:73-80. 130. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424. 131. Munro MJ, Wickremesekera SK, Peng L, et al. Cancer stem cells in colorectal cancer: a review. J Clin Pathol 2018;71:110-116. 132. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100:57-70. 133. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74. 134. Fleming M, Ravula S, Tatishchev SF, et al. Colorectal carcinoma: Pathologic aspects. J Gastrointest Oncol 2012;3:153-73. 135. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med 2009;361:2449-60. 136. Vogelstein B, Fearon ER, Hamilton SR, et al. Genetic alterations during colorectal-tumor development. N Engl J Med 1988;319:525-32. 137. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990;61:759-67. 138. Preston SL, Wong WM, Chan AO, et al. Bottom-up histogenesis of colorectal adenomas: origin in the monocryptal adenoma and initial expansion by crypt fission. Cancer Res 2003;63:3819-25. 139. Shih IM, Wang TL, Traverso G, et al. Top-down morphogenesis of colorectal tumors. Proc Natl Acad Sci U S A 2001;98:2640-5. 140. de Sousa e Melo F, Kurtova AV, Harnoss JM, et al. A distinct role for Lgr5(+) stem cells in primary and metastatic colon cancer. Nature 2017;543:676-680. 141. Sottoriva A, Spiteri I, Shibata D, et al. Single-molecule genomic data delineate patient-specific tumor profiles and cancer stem cell organization. Cancer Res 2013;73:41-9. 142. Zhou Y, Xia L, Wang H, et al. Cancer stem cells in progression of colorectal cancer. Oncotarget 2018;9:33403-33415. 143. Boman BM, Huang E. Human colon cancer stem cells: a new paradigm in gastrointestinal oncology. J Clin Oncol 2008;26:2828-38. 144. Dalerba P, Dylla SJ, Park IK, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci U S A 2007;104:10158-63. 145. Abbasian M, Mousavi E, Arab-Bafrani Z, et al. The most reliable surface marker for the identification of colorectal cancer stem-like cells: A systematic review and meta-analysis. J Cell Physiol 2019;234:8192-8202. 146. Haraguchi N, Ohkuma M, Sakashita H, et al. CD133+CD44+ population efficiently enriches colon cancer initiating cells. Ann Surg Oncol 2008;15:2927-33. 147. Basakran NS. CD44 as a potential diagnostic tumor marker. Saudi Med J 2015;36:273-9. 148. Spring FA, Dalchau R, Daniels GL, et al. The Ina and Inb blood group antigens are located on a glycoprotein of 80,000 MW (the CDw44 glycoprotein) whose expression is influenced by the In(Lu) gene. Immunology 1988;64:37-43. 149. Wielenga VJ, Smits R, Korinek V, et al. Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway. Am J Pathol 1999;154:515-23. 150. Du L, Wang H, He L, et al. CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res 2008;14:6751-60. 151. Lee SY, Kim KA, Kim CH, et al. CD44-shRNA recombinant adenovirus inhibits cell proliferation, invasion, and migration, and promotes apoptosis in HCT116 colon cancer cells. Int J Oncol 2017;50:329-336. 152. Shmelkov SV, Butler JM, Hooper AT, et al. CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. J Clin Invest 2008;118:2111-20. 153. Huh JW, Kim HR, Kim YJ, et al. Expression of standard CD44 in human colorectal carcinoma: association with prognosis. Pathol Int 2009;59:241-6. 154. Gotley DC, Fawcett J, Walsh MD, et al. Alternatively spliced variants of the cell adhesion molecule CD44 and tumour progression in colorectal cancer. Br J Cancer 1996;74:342-51. 155. Choi SH, Takahashi K, Eto H, et al. CD44s expression in human colon carcinomas influences growth of liver metastases. Int J Cancer 2000;85:523-6. 156. Todaro M, Gaggianesi M, Catalano V, et al. CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis. Cell Stem Cell 2014;14:342-56. 157. Grillet F, Bayet E, Villeronce O, et al. Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture. Gut 2017;66:1802-1810. 158. Mulder JW, Kruyt PM, Sewnath M, et al. Colorectal cancer prognosis and expression of exon-v6-containing CD44 proteins. Lancet 1994;344:1470-2. 159. Saito S, Okabe H, Watanabe M, et al. CD44v6 expression is related to mesenchymal phenotype and poor prognosis in patients with colorectal cancer. Oncol Rep 2013;29:1570-8. 160. Wielenga VJ, van der Voort R, Taher TE, et al. Expression of c-Met and heparan-sulfate proteoglycan forms of CD44 in colorectal cancer. Am J Pathol 2000;157:1563-73. 161. O'Brien CA, Pollett A, Gallinger S, et al. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 2007;445:106-10. 162. Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al. Identification and expansion of human colon-cancer-initiating cells. Nature 2007;445:111-5. 163. Li YF, Xiao B, Tu SF, et al. Cultivation and identification of colon cancer stem cell-derived spheres from the Colo205 cell line. Braz J Med Biol Res 2012;45:197-204. 164. Todaro M, Francipane MG, Medema JP, et al. Colon cancer stem cells: promise of targeted therapy. Gastroenterology 2010;138:2151-62. 165. Chen T, Zhang Y, Guo WH, et al. Effects of heterochromatin in colorectal cancer stem cells on radiosensitivity. Chin J Cancer 2010;29:270-6. 166. Todaro M, Alea MP, Di Stefano AB, et al. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 2007;1:389-402. 167. Chen S, Song X, Chen Z, et al. CD133 expression and the prognosis of colorectal cancer: a systematic review and meta-analysis. PLoS One 2013;8:e56380. 168. Horst D, Kriegl L, Engel J, et al. CD133 expression is an independent prognostic marker for low survival in colorectal cancer. Br J Cancer 2008;99:1285-9. 169. Snippert HJ, van Es JH, van den Born M, et al. Prominin-1/CD133 marks stem cells and early progenitors in mouse small intestine. Gastroenterology 2009;136:2187-2194 e1. 170. Gao W, Chen L, Ma Z, et al. Isolation and phenotypic characterization of colorectal cancer stem cells with organ-specific metastatic potential. Gastroenterology 2013;145:636-46 e5. 171. He S, Zhou H, Zhu X, et al. Expression of Lgr5, a marker of intestinal stem cells, in colorectal cancer and its clinicopathological significance. Biomed Pharmacother 2014;68:507-13. 172. Uchida H, Yamazaki K, Fukuma M, et al. Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5 in colorectal cancer. Cancer Sci 2010;101:1731-7. 173. Hsu HC, Liu YS, Tseng KC, et al. Overexpression of Lgr5 correlates with resistance to 5-FU-based chemotherapy in colorectal cancer. Int J Colorectal Dis 2013;28:1535-46. 174. Shimokawa M, Ohta Y, Nishikori S, et al. Visualization and targeting of LGR5(+) human colon cancer stem cells. Nature 2017;545:187-192. 175. Wu W, Cao J, Ji Z, et al. Co-expression of Lgr5 and CXCR4 characterizes cancer stem-like cells of colorectal cancer. Oncotarget 2016;7:81144-81155. 176. Gerger A, Zhang W, Yang D, et al. Common cancer stem cell gene variants predict colon cancer recurrence. Clin Cancer Res 2011;17:6934-43. 177. Wang R, Brattain MG. AKT can be activated in the nucleus. Cell Signal 2006;18:1722-31. 178. Lee TC, Huang YC, Lu YZ, et al. Hypoxia-induced intestinal barrier changes in balloon-assisted enteroscopy. J Physiol 2018;596:3411-3424. 179. Luo Y, Tian Z, Hua X, et al. Isorhapontigenin (ISO) inhibits stem cell-like properties and invasion of bladder cancer cell by attenuating CD44 expression. Cell Mol Life Sci 2020;77:351-363. 180. Boldrup L, Coates PJ, Gu X, et al. DeltaNp63 isoforms regulate CD44 and keratins 4, 6, 14 and 19 in squamous cell carcinoma of head and neck. J Pathol 2007;213:384-91. 181. Godar S, Ince TA, Bell GW, et al. Growth-inhibitory and tumor- suppressive functions of p53 depend on its repression of CD44 expression. Cell 2008;134:62-73. 182. Yevshin I, Sharipov R, Kolmykov S, et al. GTRD: a database on gene transcription regulation-2019 update. Nucleic Acids Res 2019;47:D100-D105. 183. Cerami E, Gao J, Dogrusoz U, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2012;2:401-4. 184. Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 2013;6:pl1. 185. Cancer Genome Atlas N. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012;487:330-7. 186. Seshagiri S, Stawiski EW, Durinck S, et al. Recurrent R-spondin fusions in colon cancer. Nature 2012;488:660-4. 187. Giannakis M, Mu XJ, Shukla SA, et al. Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma. Cell Rep 2016;15:857-865. 188. Goldman M, Craft B, Hastie M, et al. The UCSC Xena platform for public and private cancer genomics data visualization and interpretation. bioRxiv 2019:326470. 189. Goldman MJ, Craft B, Hastie M, et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol 2020;38:675-678. 190. Zhao Y, Zhang W, Guo Z, et al. Inhibition of the transcription factor Sp1 suppresses colon cancer stem cell growth and induces apoptosis in vitro and in nude mouse xenografts. Oncol Rep 2013;30:1782-92. 191. Yu Y, Peng K, Li H, et al. SP1 upregulated FoxO3a promotes tumor progression in colorectal cancer. Oncol Rep 2018;39:2235-2242. 192. Albasri AM, Elkablawy MA, Ansari IA, et al. The prognostic significance of p63 cytoplasmic expression in colorectal cancer. An immunohistochemical study. Saudi Med J 2019;40:432-439. 193. Guo HQ, Huang GL, Liu OF, et al. p63 Expression is a prognostic factor in colorectal cancer. Int J Biol Markers 2012;27:e212-8. 194. Ghavam-Nasiri MR, Rezaei E, Ghafarzadegan K, et al. Expression of p53 in colorectal carcinoma: correlation with clinicopathologic features. Arch Iran Med 2007;10:38-42. 195. Wang P, Liang J, Wang Z, et al. The prognostic value of p53 positive in colorectal cancer: A retrospective cohort study. Tumour Biol 2017;39:1010428317703651. 196. Liu Y, Wang G, Yang Y, et al. Increased TEAD4 expression and nuclear localization in colorectal cancer promote epithelial-mesenchymal transition and metastasis in a YAP-independent manner. Oncogene 2016;35:2789-800. 197. Tang JY, Yu CY, Bao YJ, et al. TEAD4 promotes colorectal tumorigenesis via transcriptionally targeting YAP1. Cell Cycle 2018;17:102-109. 198. Giraud J, Molina-Castro S, Seeneevassen L, et al. Verteporfin targeting YAP1/TAZ-TEAD transcriptional activity inhibits the tumorigenic properties of gastric cancer stem cells. Int J Cancer 2020;146:2255-2267. 199. Liu Y, Wang G, Liang Z, et al. Lysyl oxidase: A colorectal cancer biomarker of lung and hepatic metastasis. Thorac Cancer 2018;9:785-793. 200. Byun MR, Hwang JH, Kim AR, et al. SRC activates TAZ for intestinal tumorigenesis and regeneration. Cancer Lett 2017;410:32-40. 201. Jiao S, Li C, Hao Q, et al. VGLL4 targets a TCF4-TEAD4 complex to coregulate Wnt and Hippo signalling in colorectal cancer. Nat Commun 2017;8:14058. 202. Gibault F, | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78063 | - |
| dc.description.abstract | 背景：肌凝蛋白輕鏈激酶（Myosin Light Chain Kinase, MLCK）由短型與長型組成，其編碼在同一個基因MYLK的蛋白，其在肌肉或非肌肉細胞中會磷酸化肌凝蛋白輕鏈（Myosin Light Chain, MLC）調控肌動凝蛋白（Actinomysin）收縮。腸道上皮細胞表現長型MLCK調節屏障功能。在大腸直腸癌（Colorectal Cancer, CRC）的檢體中發現MYLK 的低表現量。大腸直腸癌是一種固態腫瘤由高表現CD44與CD133分子的癌幹細胞（Cancer Stem Cell, CSC）所維持。目的：為了探討長型MLCK在大腸癌腫瘤生成與癌症幹性的分子機制。方法材料：來自台大醫院病患檢體被納入研究分析。三維初代大腸類器官（Organoid）從長型MLCK-210缺失（MLCK(-/-)）小鼠與野生型（Wild-type, WT）小鼠培養於基質膠（Matrigel Matrix）。人類大腸腺瘤Caco-2細胞株處理ML-7（MLCK藥物抑制劑）與由慢病毒小髮夾RNA（Short Hairpin RNA, shRNA）進行MLCK基因減弱（Knockdown, KD）技術。在人類大腸腺瘤細胞株Caco-2經由CRISPR/Cas9系統進行MYLK基因剔除（Knockout, KO）後，藉由流式細胞儀（Flow Cytometry）染上Ki-67與碘化丙啶（Propidium Iodide, PI）來評估細胞週期速率。結果：在同觀察到其較低的長型MYLK表現在腫瘤組織中相較周邊非腫瘤組織。從MLCK剔除的大腸類器官顯示尺寸較大且較高的Cd44表現於野生型小鼠的。我們使用生物資訊工具：基因轉錄調控資料庫（Gene Transcription Regulation Database, GTRD）根據染色質免疫沉澱測序實驗（Chromatin Immunoprecipitation-sequencing, ChIP-seq）建立的資料庫，發現了潛在CD44轉錄因子（Transcription Factor, TF）--TEAD4，並且使用螢光素酶測定確認TEAD4會結合在CD44啟動子上。利用兩株大腸癌細胞株Caco-2與HT-29藉由Verteporfin抑制TEAD4的功能後，其CD44表現量下降。在ML-7藥物與慢病毒載體基因減弱MLCK促使CD44與TEAD4表現提升，而不改變CD133與LGR5表現或是其他假定的轉錄因子（像是SP1, TP63 , TP53）MLCK基因剔除細胞加速細胞週期（Cell Cycle）速率，然而轉染質體MLCK於KO細胞過表現後抵銷了細胞過度增生與CD44和TEAD4表現下降。利用西方墨點法觀察到MLCK-KO細胞的細胞核會出現YAP與VGLL3蛋白量趨勢上升相較於野生型Caco-2細胞，然而轉染轉染質體MLCK1或2後，發現分別降低VGLL3與YAP於核轉移蛋白量。結論：長型MYLK是個新穎的腫瘤抑制基因，其不同的同功型（isoform）MLCK1/2藉由不同TEAD4的輔助因子(cofactor) VGLL3/YAP調控CD44表現。 | zh_TW |
| dc.description.abstract | Background: Myosin light chain kinase (MLCK), comprised of short and long isoforms encoded by a single MYLK gene, phosphorylates myosin light chain (MLC) to regulate actinomyosin contraction in muscles and nonmuscle cells. The intestinal epithelial cells express long MLCK to regulate barrier functions. Reduced MYLK transcripts were found in human colon carcinoma (CRC) specimens. CRC is a solid tumor clonally sustained by cancer stem cells (CSCs) highly expressed with CD44 and CD133 molecules. Aim: To investigate the mechanistic role of long MLCK in colon tumorigenesis and cancer stemness. Methods: Human CRC specimens collected from National Taiwan University Hospital (NTUH) were analyzed. Three-dimensional primary colonic organoids were developed from mice deficient of long MLCK-210 (MLCK(-/-)) and wild type (WT) mice by Matrigel culturing. Human colonic adenocarcinoma Caco-2 cells were administered ML-7 (an MLCK inhibitor) or gene knockdown (KD) by lentiviral shRNA. CRISPR/Cas9-based MYLK gene knockout (KO) in Caco-2 cells were assessed for cell cycle rates by flow cytometry with Ki-67 and propidium iodide (PI) staining. Results: Lower expression of long MYLK mRNA was observed in human CRC tissues than adjacent non-tumor tissues. Colonic organoids from MLCK(-/-) mice showed larger sizes and higher Cd44 expression compared to those from WT mice. We found a potential CD44 transcription factor, TEAD4, by bioinformatics analysis using Gene Transcription Regulation Database (GTRD) based on ChIP-seq experiments. We further confirmed TEAD4 as a transcription factor of CD44 using a luciferase reporter assay. Inhibition of TEAD4 function by verteporfin reduced CD44 expression in Caco-2 and HT29 cells. Administration of ML-7 and lentiviral KD of MLCK induced an elevation of CD44 and TEAD4 expression in Caco-2 cells, without changes in the CD133 and LGR5 levels or other putative transcription factors (e.g. SP1, TP63, TP53). Caco-2 cells with MLCK-KO showed accelerated cell cycle rates, whereas transfection with MLCK-encoding plasmids in the KO cells counterbalanced the cell hyperproliferation and decreased the expression of CD44 and TEAD4. Densitometric analysis of Western blots showed significantly increased YAP and a trend to increased VGLL3 in the nuclear fraction of MLCK-KO cells compared to wild type Caco-2 cells; whereas transfection with human MLCK1/2- encoding plasmids reduced the nuclear translocation of VGLL3 and YAP, respectively. Conclusion: Long MYLK is novel tumor suppressor gene of which the splice variants MLCK1/2 reduced CD44 expression through differential regulation of TEAD4 transcriptional cofactors. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T14:41:06Z (GMT). No. of bitstreams: 1 U0001-1408202017515100.pdf: 5708524 bytes, checksum: 86a94c788f093cd73ad1bc9c701a0d89 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | ACKNOWLEDGEMENTS I 中文摘要 II ABSTRACT IV LIST OF ABBREVIATIONS VI CONTENTS VII LIST OF TABLES IX LIST OF FIGURES IX INTRODUCTION 1 1. INTESTINAL CRYPTS AND INTESTINAL STEM CELLS 1 1.1 Intestinal stem cells 2 1.2 Stem cell niche 3 1.2.1 WNT 4 1.2.2 Notch 5 1.2.3 Epidermal growth factor (EGF) 6 1.2.4 Bone morphogenetic protein (BMP) 6 1.2.5 Hedgehog 7 1.2.6 Hippo pathway 8 2. MYOSIN LIGHT CHAIN KINASE IN GUT HOMEOSTASIS AND CARCINOGENESIS 10 2.1 Myosin light chain kinase (MLCK) 10 2.2 Long MLCK 11 2.3 Controversial role of MLCK in carcinogenesis 11 3. COLORECTAL CANCER (CRC) AND CANCER STEM CELLS (CSCS) 13 3.1 Colorectal carcinoma 13 3.2 Colorectal cancer stem cells 14 3.2.1 CD44 15 3.2.2 CD133 17 3.2.3 LGR5 18 4. RESEARCH AIM AND HYPOTHESIS 18 MATERIALS AND METHODS 19 1. HUMAN CLINICAL COLORECTAL CANCER BIOPSIES 19 2. EXPERIMENTAL ANIMALS 19 3. HUMAN CELL LINES 20 4. PLASMID CONSTRUCT, TRANSFORMATION AND PLASMID DNA EXTRACTION 21 5. ADMINISTRATION OF REAGENTS 22 6. GENE KNOCKOUT AND PLASMID TRANSFECTION IN HUMAN CELL LINE 23 7. GENE KNOCKDOWN BY TRANSDUCTION WITH LENTIVIRAL DELIVERY OF SHRNA 23 8. BIOINFORMATIC TOOLS 25 9. ORGANOID CULTURE AND SIZE ANALYSIS 26 10. RNA EXTRACTION, QUANTITATIVE REAL-TIME POLYMERASE CHAIN REACTION (QPCR), AND SEMIQUANTITATIVE REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION (RT-PCR) 28 11. WESTERN BLOTTING 31 11.1 Collection of whole cell lysate, and cytoplasmic and nuclear fractions of cellular proteins 31 11.2 Sodium dodecyl sulfate polyacrylamide (SDS-PAGE) gel electrophoresis 33 12. LUCIFERASE REPORTER ASSAY 35 13. CELL CYCLE ANALYSIS BY FLOW CYTOMETRY 36 14. STATISTICAL ANALYSIS 37 RESULTS 38 1. GENE EXPRESSION OF HUMAN SPECIMENS FROM CRC PATIENTS 38 2. ANALYSIS OF MYLK AND TRANSCRIPTION FACTORS OF CD44 THROUGH BIOINFORMATIC TOOLS FROM TCGA DATABASE 39 3. RAPID GROWTH AND HIGHER LEVELS OF CD44 AND TEAD4 IN COLONIC ORGANOID FROM LONG MLCK DEFICIENT MICE 40 4. INHIBITION OF MLCK ALTERS CANCER STEM CELL EXPRESSION IN VITRO 40 5. TEAD4 TRANSCRIPTIONAL ACTIVITY REGULATES CD44 EXPRESSION IN VITRO 42 6. HYPERPROLIFERATION IN MLCK-KNOCKOUT CELLS IS COUNTERBALANCED BY MLCK OVEREXPRESSION WITH REGULATION OF TEAD4/CD44 EXPRESSION 42 7. MLCK REGULATES TEAD4 ACTIVITY VIA DISTINCT TRANSCRIPTIONAL COFACTORS 43 DISCUSSION 45 TABLES 52 FIGURES 62 REFERENCES 83 | |
| dc.language.iso | en | |
| dc.subject | TEAD4 | zh_TW |
| dc.subject | VGLL3 | zh_TW |
| dc.subject | YAP | zh_TW |
| dc.subject | 大腸直腸癌 | zh_TW |
| dc.subject | 幹性 | zh_TW |
| dc.subject | 非肌肉肌凝蛋白輕鏈激酶 | zh_TW |
| dc.subject | 腫瘤抑制基因 | zh_TW |
| dc.subject | CD44 | zh_TW |
| dc.subject | YAP | en |
| dc.subject | non-muscle myosin light chain kinase | en |
| dc.subject | colorectal cancer | en |
| dc.subject | stemness | en |
| dc.subject | tumor suppressor gene | en |
| dc.subject | CD44 | en |
| dc.subject | TEAD4 | en |
| dc.subject | VGLL3 | en |
| dc.title | 腸道上皮肌凝蛋白輕鏈激酶透過調節TEAD4/CD44表現抑制腫瘤進程 | zh_TW |
| dc.title | Intestinal Epithelial Myosin Light Chain Kinase Restrains Tumor Progression Through Regulating TEAD4/CD44 Expression | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.advisor-orcid | 余佳慧(0000-0003-1461-3249) | |
| dc.contributor.oralexamcommittee | 林泰元(THAI-YEN LING),林本仁(BEEN-REN LIN),賴亮全(LIANG-CHUAN LAI) | |
| dc.contributor.oralexamcommittee-orcid | 林泰元(0000-0002-3992-883X),林本仁(0000-0001-8354-1758),賴亮全(0000-0002-3913-5338) | |
| dc.subject.keyword | 非肌肉肌凝蛋白輕鏈激酶,大腸直腸癌,幹性,腫瘤抑制基因,CD44,TEAD4,VGLL3,YAP, | zh_TW |
| dc.subject.keyword | non-muscle myosin light chain kinase,colorectal cancer,stemness,tumor suppressor gene,CD44,TEAD4,VGLL3,YAP, | en |
| dc.relation.page | 97 | |
| dc.identifier.doi | 10.6342/NTU202003473 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-08-18 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生理學研究所 | zh_TW |
| dc.date.embargo-lift | 2025-08-17 | - |
| 顯示於系所單位： | 生理學科所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-1408202017515100.pdf 未授權公開取用 | 5.57 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。