LATS2 induced by TNF-alpha and inhibited cell proliferation and invasion by phosphorylating YAP in oral squamous cell carcinoma

J Oral Pathol Med. 2015 Jul;44(6):475-81. doi: 10.1111/jop.12317. Epub 2015 Mar 17.

Abstract

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.

Keywords: LATS2; YAP; oral squamous cell carcinoma; tumor necrosis factor-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Transformation, Neoplastic / drug effects
  • HEK293 Cells
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Nuclear Proteins / metabolism*
  • Phosphorylation / drug effects
  • Protein Serine-Threonine Kinases / biosynthesis*
  • Protein Serine-Threonine Kinases / genetics
  • Signal Transduction
  • Squamous Cell Carcinoma of Head and Neck
  • Tongue Neoplasms / drug therapy*
  • Tongue Neoplasms / metabolism
  • Tongue Neoplasms / pathology
  • Transcription Factors / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics

Substances

  • Cell Cycle Proteins
  • Nuclear Proteins
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Proteins
  • YY1AP1 protein, human
  • LATS2 protein, human
  • Protein Serine-Threonine Kinases