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

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

Author information

1
Institute for Research in Biomedicine (IRB Barcelona), 08028 Barcelona, Spain.
2
Department of Histology and Embryology, School of Medicine, University of Athens, Athens 11527, Greece.
3
Department of Histology and Embryology, School of Medicine, University of Athens, Athens 11527, Greece; Biomedical Research Foundation of the Academy of Athens, Athens 11527, Greece.
4
Institute for Research in Biomedicine (IRB Barcelona), 08028 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain. Electronic address: angel.nebreda@irbbarcelona.org.

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.

PMID:
24684847
DOI:
10.1016/j.ccr.2014.02.019
[Indexed for MEDLINE]
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