The miR-487b-3p/GRM3/TGFβ signaling axis is an important regulator of colon cancer tumorigenesis.

ABSTRACT: Molecular targeting is an import strategy to treat advanced colon cancer. The current study demonstrates that expression of GRM3, a metabotropic glutamate receptor mainly expressed in mammalian central nervous system, is significantly upregulated in majority of human colonic adenocarcinomas tested and colon cancer cell lines. Knockdown of GRM3 expression or inhibition of GRM3 activation in colon cancer cells reduces cell survival and anchorage-independent growth in vitro and inhibits tumor growth in vivo. Mechanistically, GRM3 antagonizes TGFβ-mediated activation of protein kinase A and inhibition of Protein kinase B (AKT). In addition, TGFβ signaling increases GRM3 protein stability and knockdown of GRM3 enhances TGFβ-mediated tumor suppressor function. Further studies indicate that miR-4

SUBMITTER: Yi H 

PROVIDER: S-EPMC5472494 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature