Loss of Bcl-G, a Bcl-2 family member, augments the development of inflammation-associated colorectal cancer

Cell Death Differ. 2020 Feb;27(2):742-757. doi: 10.1038/s41418-019-0383-9. Epub 2019 Jul 11.

Abstract

Gastrointestinal epithelial cells provide a selective barrier that segregates the host immune system from luminal microorganisms, thereby contributing directly to the regulation of homeostasis. We have shown that from early embryonic development Bcl-G, a Bcl-2 protein family member with unknown function, was highly expressed in gastrointestinal epithelial cells. While Bcl-G was dispensable for normal growth and development in mice, the loss of Bcl-G resulted in accelerated progression of colitis-associated cancer. A label-free quantitative proteomics approach revealed that Bcl-G may contribute to the stability of a mucin network, which when disrupted, is linked to colon tumorigenesis. Consistent with this, we observed a significant reduction in Bcl-G expression in human colorectal tumors. Our study identifies an unappreciated role for Bcl-G in colon cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / metabolism
  • Colitis / pathology
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Humans
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Mice
  • Mice, Knockout
  • Proto-Oncogene Proteins c-bcl-2 / deficiency
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*

Substances

  • BCL2L14 protein, human
  • Proto-Oncogene Proteins c-bcl-2