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Updated: May 31, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Enormous influence of TNIK knockdown on intracellular signals and cell survival
Jinghua Gui1, Baotian Yang, Jinyun Wu
1Xinyuan Institute of Medicine and Biotechnology, College of Life Science, Zhejiang Sci-Tech University, Room 201, Building No. 6, Xiasha, Hangzhou 310018, China.
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.
Insights
Traf2- and Nck-interacting kinase (TNIK) is crucial for Wnt and c-Jun N-terminal kinase (JNK) pathway activation. TNIK knockdown in colon cancer cells inhibits cell proliferation and triggers apoptosis, highlighting its pro-survival role.
Area of Science:
- Cellular signaling pathways
- Molecular biology
- Cancer research
Background:
- Intracellular signals regulate cell activities, with Wnt signaling impacting tissue polarity and cell movement via the c-Jun N-terminal kinase (JNK) pathway.
- Traf2- and Nck-interacting kinase (TNIK) is a key transcription factor mediating Wnt target gene activation and JNK pathway activity.
Purpose of the Study:
- To investigate the function of TNIK in colon cancer by examining its role in intracellular signaling pathways.
- To elucidate the impact of TNIK modulation on Wnt and JNK signaling, gene expression, and apoptosis in colon cancer cells.
Main Methods:
- Short-hairpin RNA (shRNA)-mediated knockdown of TNIK in colon cancer cell lines.
- Analysis of gene expression (CD44, c-MYC, cyclin D1) and TCF-4 reporter activity.
- Assessment of JNK1/JNK2 activation by TNFα and AP1 luciferase activity.
- Adenovirus-mediated TNIK downregulation to induce apoptosis via caspase-9 and PARP-1 activation.
Main Results:
- TNIK knockdown reduced CD44, c-MYC, and cyclin D1 expression, correlating with TCF-4 reporter assay results.
- TNIK knockdown inhibited TNFα-induced activation of JNK1 and JNK2, subsequently reducing AP1 luciferase activity.
- Adenovirus-mediated TNIK downregulation induced intrinsic apoptosis in SW480 cells by activating caspase-9 and PARP-1.
Conclusions:
- TNIK is essential for activating both the canonical Wnt and JNK signaling pathways.
- TNIK functions as a pro-survival factor in colon cancer cells.
- Targeting TNIK presents a potential therapeutic strategy for colon cancer by disrupting key survival pathways.
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