WDR76 degrades RAS and suppresses cancer stem cell activation in colorectal cancer.

ABSTRACT:

Background

Stabilization of RAS is a key event for the hyper-activation of Wnt/β-catenin signaling and activation of cancer stem cell (CSC) in colorectal cancer (CRC). WD Repeat protein 76 (WDR76) mediates the polyubiquitination-dependent degradation of RAS in hepatocellular carcinoma (HCC). We investigated whether WDR76 destabilizes RAS and acts as a tumor suppressor inhibiting CSC activation in CRC.

Methods

We generated mice with deletion of Wdr76 (Wdr76^-/-) and crosses of Wdr76^-/- with Apc^Min/+ (Wdr76^-/-; Apc^Min/+) and compared them with wildtype mice (Wdr76^+/+) and Apc^Min/+ mice (Wdr76^+/+; Apc^Min/+), respectively. Intestinal crypt lengthening, tumorigenesis and CSC activati

SUBMITTER: Ro EJ 

PROVIDER: S-EPMC6668196 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature