LATS2 induced by TNF-alpha and inhibited cell proliferation and invasion by phosphorylating YAP in oral squamous cell
Cong Dong1,2, Kui-Jie Wei3, Wen-Bin Zhang1
1Shanghai Key Laboratory of Stomatology, Department of Oral and Cranio-Maxillofacial Science, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Objective:
Many reports indicated LATS2 was a component of the Hippo pathway, could phosphorylate and inactivate YAP, acted as a tumor suppressor in human cancers. But few studies investigated the role of LATS2 in oral squamous cell carcinoma (OSCC) and clarified the mechanisms of regulation of LATS2 expression.
Design:
The expressions of LATS2 and phosphorylated YAP were detected by Western blotting in HN6 cells treated with TNF-α in different time and different dose. Luciferase reporter assays were performed to detect whether YAP can be phosphorylated by LATS2 in HN6 cells. Cell proliferation, anchorage independent growth in soft agar, transwell cell invasion assay, and nu mice in vivo xenografts growth were performed to study the effects of overexpression of LATS2 on OSCC cells.
Results:
In this study, we confirmed that YAP can be phosphorylated by LATS2. LATS2 can be dose- and time-dependently induced by TNF-α in HN6 cells. Overexpression of LATS2 inhibited cell proliferation, colony formation, cell invasion, and in vivo xenografts growth in OSCC cells.
Conclusion:
LATS2 could be induced by TNF-alpha and inhibited cell proliferation and invasion by phosphorylating YAP in OSCC cells. LATS2 might play a role in the tumorigenesis of OSCC and might be a potential therapeutic target in OSCC treatment.
Insights
Large tumor suppressor 2 (LATS2) inhibits oral squamous cell carcinoma (OSCC) progression by phosphorylating YAP. Tumor necrosis factor-alpha (TNF-α) induces LATS2, suggesting LATS2 as a potential therapeutic target for OSCC.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Large tumor suppressor 2 (LATS2) is a known Hippo pathway component that phosphorylates and inactivates YAP, acting as a tumor suppressor in various human cancers.
- The specific role and regulatory mechanisms of LATS2 in oral squamous cell carcinoma (OSCC) remain underexplored.
Purpose of the Study:
- To investigate the role of LATS2 in OSCC.
- To elucidate the mechanisms regulating LATS2 expression in OSCC.
- To determine the functional impact of LATS2 on OSCC cell behavior.
Main Methods:
- Western blotting to detect LATS2 and phosphorylated YAP expression in HN6 cells treated with TNF-α.
- Luciferase reporter assays to confirm YAP phosphorylation by LATS2.
- Assays for cell proliferation, anchorage-independent growth, invasion, and in vivo xenograft growth to assess the effects of LATS2 overexpression.
Main Results:
- LATS2 was confirmed to phosphorylate YAP.
- TNF-α dose- and time-dependently induced LATS2 expression in HN6 cells.
- Overexpression of LATS2 significantly inhibited OSCC cell proliferation, colony formation, invasion, and in vivo tumor growth.
Conclusions:
- LATS2, induced by TNF-α, inhibits OSCC cell proliferation and invasion via YAP phosphorylation.
- LATS2 plays a critical role in OSCC tumorigenesis.
- LATS2 represents a potential therapeutic target for OSCC treatment.
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