title: TR1 promotes cell proliferation and inhibits apoptosis through cyclin A and CTGF regulation in non-small cell lung cancer.
abstract: The Hippo pathway plays a major role in development and organ size control, and its dysregulation contributes to tumorigenesis. WWTR1 is a transcription coactivator acting downstream of the Hippo pathway. Recently, WWTR1 has been reported to be overexpressed in several human cancers including lung cancer. However, the molecular mechanism of WWTR1 regulating lung cancer aggressiveness remains ambiguous. In the present study, we analyzed the expression of WWTR1 in NSCLC cell lines and found that WWTR1 was overexpressed at both the mRNA and protein levels. Knockdown of WWTR1 by siRNA interference in A549 cells significantly inhibited cell proliferation and increased paclitaxel-induced apoptosis. On the other side, WWTR1 overexpression in HBE cell line promoted cell proliferation and inhibited apoptosis. In addition, we found that the decreased proliferation after siRNA treatment was due to cell cycle arrest. Further analysis showed that WWTR1 could induce cyclin A, connective tissue growth factor (CTGF) expression, and inhibit caspase3 cleavage. In conclusion, WWTR1 promotes malignant cell growth and inhibits apoptosis by cyclin A and CTGF regulation.
authors: Li
authors: L
authors: Wang
authors: Zhenhong
authors: Z
authors: Chen
authors: Yajuan
authors: Y
authors: Wang
authors: De
authors: D
authors: Chang
authors: Longxiang
authors: L
authors: Su
authors: Yinghua
authors: Y
authors: Guo
authors: Changting
authors: C
authors: Liu
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D055513:Connective Tissue Growth Factor / Q000235:genetics* / Q000378:metabolism; D019925:Cyclin A / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins
chemical_list: D019925:Cyclin A; D047908:Intracellular Signaling Peptides and Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D055513:Connective Tissue Growth Factor; D053148:Caspase 3
references: Am J Pathol. 2000 Jun;156(6):2135-47
references: 10854234
references: Prog Cell Cycle Res. 1995;1:115-23
references: 9552357
references: Tumour Biol. 2011 Apr;32(2):335-46
references: 21113745
references: J Thorac Oncol. 2012 May;7(5):799-807
references: 22481233
references: J Biol Chem. 2012 Jul 27;287(31):26245-53
references: 22692215
references: Int J Biochem Cell Biol. 2009 Apr;41(4):771-83
references: 18775791
references: Carcinogenesis. 2012 Jan;33(1):59-67
references: 22045023
references: Tumour Biol. 2012 Aug;33(4):1053-8
references: 22290426
references: Tumour Biol. 2011 Aug;32(4):721-8
references: 21503841
references: Oncogene. 2011 Feb 3;30(5):600-10
references: 20972459
references: Oncol Rep. 2012 Jul;28(1):179-85
references: 22470139
references: Cancer Surv. 1997;29:7-23
references: 9338094
references: Prog Growth Factor Res. 1991;3(4):267-77
references: 1839823
references: Curr Opin Genet Dev. 1993 Feb;3(1):11-8
references: 8384033
references: Cancer Res. 2008 Apr 15;68(8):2592-8
references: 18413727
references: Cell Mol Life Sci. 2002 Aug;59(8):1317-26
references: 12363035
references: Cancer Res. 2011 Apr 1;71(7):2728-38
references: 21349946
references: PLoS One. 2013;8(1):e54211
references: 23372686
references: Eur J Cancer. 2011 Apr;47(6):926-33
references: 21131195
references: Oncogene. 2011 May 5;30(18):2181-6
references: 21258416
references: J Biomed Sci. 2008 Nov;15(6):675-85
references: 18622762