title: Dual function of p38α MAPK in colon cancer: suppression of colitis-associated tumor initiation but requirement for cancer cell survival.
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.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), 08028 Barcelona, Spain.
authors.forename: Jalaj
authors.initials: J
authors.lastname: Gupta
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), 08028 Barcelona, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: del Barco Barrantes
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), 08028 Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Igea
authors.affiliation: Department of Histology and Embryology, School of Medicine, University of Athens, Athens 11527, Greece.
authors.forename: Stratigoula
authors.initials: S
authors.lastname: Sakellariou
authors.affiliation: Department of Histology and Embryology, School of Medicine, University of Athens, Athens 11527, Greece.
authors.forename: Ioannis S
authors.initials: IS
authors.lastname: Pateras
authors.affiliation: 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.
authors.forename: Vassilis G
authors.initials: VG
authors.lastname: Gorgoulis
authors.affiliation: 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.
authors.forename: Angel R
authors.initials: AR
authors.lastname: Nebreda
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D003092:Colitis / Q000201:enzymology* / Q000473:pathology; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015536:Down-Regulation; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D048308:Mitogen-Activated Protein Kinase 14