Loss of the 14-3-3? is essential for LASP1-mediated colorectal cancer progression via activating PI3K/AKT signaling pathway.

ABSTRACT: LIM and SH3 protein 1 (LASP1) can promote colorectal cancer (CRC) progression and metastasis, but the direct evidence that elucidates the molecular mechanism remains unclear. Here, our proteomic data showed that LASP1 interacted with 14-3-3? and decreased the expression of 14-3-3? in CRC. Deletion of 14-3-3? was required for LASP1-mediated CRC cell aggressiveness. In vitro gain- and loss-of-function assays showed that 14-3-3? suppressed the ability of cell migration and decreased the phosphorylation of AKT in CRC cells. We further observed clearly co-localization between AKT and 14-3-3? in CRC cells. Treatment of PI3K inhibitor LY294002 markedly prevented phosphorylation of AKT and subsequently counteract aggressive phenotype mediated by siRNA of 14-3-3?. Clinically, 14-3-3? is frequently down-regulated in CRC tissues. Down-regulation of 14-3-3? is associated with tumor progression and poor prognosis of patients with CRC. Multivariate analysis confirmed low expression of 14-3-3? as an independent prognostic factor for CRC. A combination of low 14-3-3? and high LASP1 expression shows a worse trend with overall survival of CRC patients. Our research paves the path to future investigation of the LASP1-14-3-3? axis as a target for novel anticancer therapies of advanced CRC.

SUBMITTER: Shao Z 

PROVIDER: S-EPMC4860602 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature