title: Loss of the 14-3-3σ 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 14-3-3σ 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.
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ziyun
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Department of Gerontology, Guangzhou General Hospital of the Guangzhou Military Command of the People's Liberation Army (PLA), Guangzhou, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xu
authors.affiliation: The Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jiaolong
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Kehong
authors.initials: K
authors.lastname: Zheng
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Fengliu
authors.initials: F
authors.lastname: Deng
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Lanzhi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Affiliated Tumor Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Radiotherapy Department, Affiliated Tumor Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Mingyi
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D018450:Disease Progression; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D060588:LIM Domain Proteins / Q000378:metabolism*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D048948:14-3-3 Proteins; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C096353:LASP1 protein, human; D060588:LIM Domain Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt