Targeting p38γ to inhibit human colorectal cancer cell progression

Biochem Biophys Res Commun. 2019 Sep 10;517(1):172-179. doi: 10.1016/j.bbrc.2019.07.038. Epub 2019 Jul 23.

Abstract

Colorectal cancer (CRC) is a common malignancy globally causing significant cancer-related mortality. Recent studies have proposed p38gamma (p38γ) as a novel cyclin-dependent kinase (CDK)-like kinase, promoting tumorigenesis and cancer progression. The current study evaluates p38γ expression and potential role in CRC. In HT-29 cells and primary human colon cancer cells, shRNA-induced p38γ silencing or CRISPR/Cas9-mediated p38γ knockout inhibited cell growth, proliferation, and migration, and induced significant apoptosis. Conversely, ectopic overexpression of p38γ further promoted the growth, proliferation, and migration of HT-29 cells and primary colon cancer cells. Retinoblastoma (Rb) phosphorylation and cyclins (E1/A) expression were decreased by p38γ silencing or KO, but increased with p38γ overexpression. p38γ mRNA and protein levels are significantly upregulated in human colon cancer tissues, when compared to levels in surrounding colon epithelial tissues. These results demonstrate that overexpression of p38γ can promote human CRC cell progression, and identify p38γ as a novel therapeutic target.

Keywords: Colorectal cancer; Molecular targets; p38γ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing*
  • HT29 Cells
  • Humans
  • Mitogen-Activated Protein Kinase 12 / genetics*

Substances

  • Mitogen-Activated Protein Kinase 12