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

• Published in: Scientific reports 2016-05, Vol.6, p.25631
• Main Authors: Shao, Ziyun, Cai, Yanjun, Xu, Lijun, Yao, Xueqing, Shi, Jiaolong, Zhang, Feifei, Luo, Yuhao, Zheng, Kehong, Liu, Jian, Deng, Fengliu, Li, Rui, Zhang, Lanzhi, Wang, Hui, Li, Mingyi, Ding, Yanqing, Zhao, Liang
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 14-3-3 protein; AKT protein; Cell migration; Clonal deletion; Colorectal cancer; Colorectal carcinoma; Localization; Medical prognosis; Metastases; Multivariate analysis; Phosphorylation; Signal transduction; siRNA
• ISSN: 2045-2322
• DOI: 10.1038/srep25631

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 14-3-3σ and decreased the expression of 14-3-3σ in CRC. Deletion of 14-3-3σ was required for LASP1-mediated CRC cell aggressiveness. In vitro gain- and loss-of-function assays showed that 14-3-3σ suppressed the ability of cell migration and decreased the phosphorylation of AKT in CRC cells. We further observed clearly co-localization between AKT and 14-3-3σ in CRC cells. Treatment of PI3K inhibitor LY294002 markedly prevented phosphorylation of AKT and subsequently counteract aggressive phenotype mediated by siRNA of 14-3-3σ. Clinically, 14-3-3σ is frequently down-regulated in CRC tissues. Down-regulation of 14-3-3σ is associated with tumor progression and poor prognosis of patients with CRC. Multivariate analysis confirmed low expression of 14-3-3σ as an independent prognostic factor for CRC. A combination of low 14-3-3σ and high LASP1 expression shows a worse trend with overall survival of CRC patients. Our research paves the path to future investigation of the LASP1-14-3-3σ axis as a target for novel anticancer therapies of advanced CRC.