DOC-2/DAB2 interactive protein destabilizes c-Myc to impair the growth and self-renewal of colon tumor-repopulating cells.

ABSTRACT: Colorectal carcinoma (CRC) remains a huge challenge in clinical treatment due to tumor metastasis and recurrence. Stem cell-like colon tumor-repopulating cells (TRCs) are a subpopulation of cancer cells with highly tumorigenic and chemotherapy resistant properties. The core transcription factor c-Myc is essential for maintaining cancer stem-like cell phenotypes, yet its roles and regulatory mechanisms remain unclear in colon TRCs. We report that elevated c-Myc protein supported formation and growth of TRC spheroids. The tumor suppressor DOC-2/DAB2 interactive protein (DAB2IP) suppressed c-Myc expression to inhibit TRC expansion and self-renewal. Particularly, DAB2IP disrupted c-Myc stability through glycogen synthase kinase 3β/protein phosphatase 2A-B56α-mediated phosphorylation and dephos

SUBMITTER: Li H 

PROVIDER: S-EPMC8586666 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature