TRPV4 induces apoptosis via p38 MAPK in human lung cancer cells
Yanyan Zhao1, Jiaying Wang1, Xuehui Liu1
1Department of Respiratory Medicine, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Abstract:
Lung cancer is one of the most common cancers worldwide. TRPV4 belongs to the 'transient receptor potential' (TRP) superfamily. It has been identified to profoundly affect a variety of physiological processes, including nociception, heat sensation, and inflammation. Unlike other TRP superfamily channels, its roles in cancers are unknown. Here, we elucidated the effects of TRPV4 and molecular mechanisms in human lung cancer cells. The levels of TRPV4 were detected in human lung cancer tissues and the paired paracarcinoma tissues by real-time PCR and western blotting analysis. The proliferation of human lung cancer cells was determined by MTT assay. Cell apoptosis was determined by FACS assay. The results demonstrated that low levels of TRPV4 were detected in clinical lung carcinoma specimens. Over-expression of TRPV4 induced cell death and inhibited cell proliferation and migration in A549 cells and H460 cells. Moreover, over-expression of TRPV4 enhanced the activation of p38 MAPK signal pathway. Inhibition of p38 MAPK abolished the effects of TRPV4 on cell proliferation, apoptosis, and migration in A549 cells. Collectively, our findings indicated that TRPV4 induced apoptosis via p38 MAPK in human lung cancer cells and suggested that TRPV4 was a potential target for therapy of human lung cancers.
Insights
Transient Receptor Potential Vanilloid 4 (TRPV4) is downregulated in lung cancer. Overexpressing TRPV4 induces apoptosis and inhibits proliferation via the p38 MAPK pathway, suggesting TRPV4 as a potential lung cancer therapy target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Lung cancer is a leading global malignancy.
- Transient Receptor Potential Vanilloid 4 (TRPV4) is involved in physiological processes but its role in cancer is largely unknown.
- Understanding TRPV4's function in lung cancer is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the role and molecular mechanisms of TRPV4 in human lung cancer cells.
- To determine the expression levels of TRPV4 in lung cancer tissues.
- To evaluate the impact of TRPV4 on cancer cell proliferation, apoptosis, and migration.
Main Methods:
- Real-time PCR and Western blotting to assess TRPV4 expression in clinical specimens.
- MTT assay to measure cell proliferation.
- FACS assay for apoptosis analysis.
- Investigated the involvement of the p38 MAPK signaling pathway.
Main Results:
- Lower TRPV4 levels were observed in lung carcinoma tissues compared to adjacent normal tissues.
- Overexpression of TRPV4 significantly inhibited proliferation and migration while inducing apoptosis in lung cancer cell lines (A549 and H460).
- TRPV4 overexpression activated the p38 MAPK pathway, and its inhibition abolished TRPV4's effects on cell behavior.
Conclusions:
- TRPV4 induces apoptosis in human lung cancer cells through the p38 MAPK signaling pathway.
- TRPV4 acts as a tumor suppressor in lung cancer.
- TRPV4 represents a promising therapeutic target for human lung cancers.
Related Concept Videos
01:31The Intrinsic Apoptotic Pathway
01:17The Extrinsic Apoptotic Pathway
01:07MAPK Signaling Cascades
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...