title: Enormous influence of TNIK knockdown on intracellular signals and cell survival.
abstract: Basic cellular activities and coordinated cell actions are governed by intracellular signals, among which the Wnt signaling cascade plays an important role in tissue polarity and cell adhesion or movement through the activation of c-Jun N-terminal kinase (JNK) pathway. As one of the central transcriptional factors, Traf2- and Nck-interacting kinase (TNIK) mediates the transactivation of Wnt target genes and promotes the activity of c-Jun N-terminus kinase (JNK)2 when overexpressed. To further understand the function of TNIK, changes in intracellular signals were detected in colon cancer cell lines using a knockdown strategy. In this study, we found that the short-hairpin RNA-mediated knockdown of TNIK decreased the expressions of CD44, c-MYC and cyclin D1, which was consistent with the results of a TCF-4 reporter assay. Our data showed, for the first time, that the activation of both JNK1 and JNK2 by TNFα could be blocked through TNIK knockdown, which dampened the AP1 luciferase activity accordingly. In addition, adenovirus mediated the downregulation of TNIK-triggered intrinsic apoptosis in SW480 cells by activating caspase-9 and PARP-1. We conclude that TNIK is essential for the activation of both the canonical Wnt pathway and the JNK pathway, and serves as a pro-survival factor.
authors.affiliation: Xinyuan Institute of Medicine and Biotechnology, College of Life Science, Zhejiang Sci-Tech University, Room 201, Building No. 6, Xiasha, Hangzhou 310018, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Gui
authors.forename: Baotian
authors.initials: B
authors.lastname: Yang
authors.forename: Jinyun
authors.initials: J
authors.lastname: Wu
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002468:Cell Physiological Phenomena / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D015179:Colorectal Neoplasms / Q000473:pathology; D055785:Gene Knockdown Techniques; D000081410:Germinal Center Kinases; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000235:genetics* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology*; D034741:RNA, Small Interfering; D060449:Wnt Signaling Pathway / Q000235:genetics* / Q000502:physiology
chemical_list: D000081410:Germinal Center Kinases; D034741:RNA, Small Interfering; D017346:Protein Serine-Threonine Kinases; C000631454:TNIK protein, human; D048031:JNK Mitogen-Activated Protein Kinases