P38γ MAPK is required for inflammation-associated colon tumorigenesis

N. Yin, X. Qi, S. Tsai, Y. Lu, Z. Basir, Kiyoko Oshima, J. P. Thomas, C. R. Myers, G. Stoner, G. Chen

Research output: Contribution to journalArticle

Abstract

Chronic inflammation has long been considered to causatively link to colon cancer development. However, signal transduction pathways involved remain largely unidentified. Here, we report that p38γ mitogen-activated protein kinase mediates inflammatory signaling to promote colon tumorigenesis. Inflammation activates p38γ in mouse colon tissues and intestinal epithelial cell-specific p38γ knockout (KO) attenuates colitis and inhibits pro-inflammatory cytokine expression. Significantly, p38γ KO inhibits tumorigenesis in a colitis-associated mouse model. The specific p38γ pharmacological inhibitor pirfenidone also suppresses pro-inflammatory cytokine expression and colon tumorigenesis. The tumor-promoting activity of epithelial p38γ was further demonstrated by xenograft studies. In addition, p38γ is required for β-catenin/Wnt activities and p38γ stimulates Wnt transcription by phosphorylating β-catenin at Ser605. These results show that p38γ activation links inflammation and colon tumorigenesis. Targeting p38γ may be a novel strategy for colon cancer prevention and treatment.

Original languageEnglish (US)
Pages (from-to)1039-1048
Number of pages10
JournalOncogene
Volume35
Issue number8
DOIs
StatePublished - Feb 25 2016
Externally publishedYes

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p38 Mitogen-Activated Protein Kinases
Colon
Carcinogenesis
Inflammation
Catenins
Colitis
Colonic Neoplasms
Cytokines
Heterografts
Signal Transduction
Epithelial Cells
Pharmacology
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Yin, N., Qi, X., Tsai, S., Lu, Y., Basir, Z., Oshima, K., ... Chen, G. (2016). P38γ MAPK is required for inflammation-associated colon tumorigenesis. Oncogene, 35(8), 1039-1048. https://doi.org/10.1038/onc.2015.158

P38γ MAPK is required for inflammation-associated colon tumorigenesis. / Yin, N.; Qi, X.; Tsai, S.; Lu, Y.; Basir, Z.; Oshima, Kiyoko; Thomas, J. P.; Myers, C. R.; Stoner, G.; Chen, G.

In: Oncogene, Vol. 35, No. 8, 25.02.2016, p. 1039-1048.

Research output: Contribution to journalArticle

Yin, N, Qi, X, Tsai, S, Lu, Y, Basir, Z, Oshima, K, Thomas, JP, Myers, CR, Stoner, G & Chen, G 2016, 'P38γ MAPK is required for inflammation-associated colon tumorigenesis', Oncogene, vol. 35, no. 8, pp. 1039-1048. https://doi.org/10.1038/onc.2015.158
Yin, N. ; Qi, X. ; Tsai, S. ; Lu, Y. ; Basir, Z. ; Oshima, Kiyoko ; Thomas, J. P. ; Myers, C. R. ; Stoner, G. ; Chen, G. / P38γ MAPK is required for inflammation-associated colon tumorigenesis. In: Oncogene. 2016 ; Vol. 35, No. 8. pp. 1039-1048.
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