PHLPP is a negative regulator of RAF1, which reduces colorectal cancer cell motility and prevents tumor progression in mice.

ABSTRACT:

Background & aims

Hyperactivation of the RAS-RAF signaling pathway in colorectal tumors is associated with metastasis and poor outcomes of patients. Little is known about how RAS-RAF signaling is turned off once activated. We investigated how the pH domain and leucine-rich repeat protein phosphatases (PHLPPs) control RAS-RAF signaling and colorectal cancer (CRC) development.

Methods

We used co-immunoprecipitation assays to identify substrates of PHLPP1 and PHLPP2. We studied phosphorylation of RAF1 in CRC cells that express exogenous PHLPP1 or PHLPP2, or lentiviral-based small hairpin RNAs against their transcripts; we measured effects on cell motility, migration, and invasion in vitro. Tumor progression and survival were analyzed in Phlpp1(-/-) Apc(Min) and Apc(Min)/Phlpp1(

SUBMITTER: Li X 

PROVIDER: S-EPMC3992173 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature