title: Ski regulates Smads and TAZ signaling to suppress lung cancer progression.
abstract: Ski, the transforming protein of the avian Sloan-Kettering retrovirus, displays both pro- and anti-oncogenic activities in human cancer. The mechanisms underlying these conflicting observations have not been fully understood. Herein, we investigated the mechanism underlying the tumor suppressor activity of Ski. To investigate the effect of Ski re-activation on TGF-β and Hippo/TAZ pathway, we measured its effect on the endogenous Smad target genes (PAI-1 and P15INK4B) and TAZ target gene CTGF. The results revealed that Ski exerted its inhibitory activity in TGF-β1/Smad signaling pathway. Ski inhibited TAZ by increasing their phosphorylation by Lats2 and did not alter the localization of TAZ. Ski inhibited lung cancer growth and invasion. Ski methylation correlated with decreased mRNA expression in human lung cancer cell lines. Thus, Ski inhibited the function of TGF-β and TAZ through multiple mechanisms in human lung cancer.
authors.affiliation: China State Key Laboratory of Respiratory Disease and Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Mian
authors.identifier: 0000-0002-5013-6673
authors.initials: M
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Oncology in Southern China, Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: China State Key Laboratory of Respiratory Disease and Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Jiexia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: China State Key Laboratory of Respiratory Disease and Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Xiangxiang
authors.initials: X
authors.lastname: Li
mesh_terms: D000072283:A549 Cells; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D051785:Smad Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; C060614:SKI protein, human
keywords: TAZ; TGF-β; YAP; lung cancer; ski