Dual function of p38α MAPK in colon cancer: suppression of colitis-associated tumor initiation but requirement for cancer cell survival

Cancer Cell. 2014 Apr 14;25(4):484-500. doi: 10.1016/j.ccr.2014.02.019. Epub 2014 Mar 27.

Abstract

Colorectal cancer is frequently associated with chronic inflammation, with the intestinal epithelial barrier playing an important protective role against the infections and injuries that cause colitis. The p38α pathway regulates inflammatory responses but can also suppress tumor initiation in epithelial cells. We have found that p38α signaling has a dual function in colorectal tumorigenesis. On one side, p38α protects intestinal epithelial cells against colitis-associated colon cancer by regulating intestinal epithelial barrier function. Accordingly, p38α downregulation results in enhanced colitis-induced epithelial damage and inflammation, which potentiates colon tumor formation. Surprisingly, inhibition of p38α in transformed colon epithelial cells reduces tumor burden. Thus, p38α suppresses inflammation-associated epithelial damage and tumorigenesis but contributes to the proliferation and survival of tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Growth Processes / physiology
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Colitis / enzymology*
  • Colitis / pathology
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Down-Regulation
  • Humans
  • MAP Kinase Signaling System
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinase 14 / metabolism*
  • Survival Analysis

Substances

  • Mitogen-Activated Protein Kinase 14