Cytosolic phospholipase A2α modulates cell-matrix adhesion via the FAK/paxillin pathway in hepatocellular carcinoma

作     者：Piao Guo Yuchao He Lu Chen Lisha Qi Dongming Liu Ziye Chen Manyu Xiao Liwei Chen Yi Luo Ning Zhang Hua Guo 

作者机构：Department of Tumor Cell Biology Department of Hepatobiliary Cancer Department of Pathology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer/ Key Laboratory of Cancer Prevention and Therapy Tianjin Tianjin's Clinical Research Center for Cancer Tianjin 300060 China 

出 版 物：《Cancer Biology & Medicine》 (癌症生物学与医学（英文版）)

年 卷 期：2019年第16卷第2期

页      面：377-390页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by grants from Key Project of Tianjin Natural Science Foundation (Grant No.18JCZDJC35200) NSFC-FRQS program (Grant No.81661128009) The Science & Technology Development Fund of Tianjin Education Commission for Higher Education (Grant No.2017KJ202) Scientific Research Foundation for Returned Scholars and Doctoral Program of Tianjin Medical University Cancer Institute and Hospital (Grant No.B1703) 

主　　题：Hepatocellular carcinoma cytosolic phospholipase A2α cell-matrix adhesion FAK paxillin 

摘      要：Objective: To explore the effect of cytosolic phospholipase A2α(cPLA2α) on hepatocellular carcinoma(HCC) cell adhesion and the underlying ***: Cell adhesion, detachment, and hanging-drop assays were utilized to examine the effect of cPLA2α on the cell-matrix and cell-cell adhesion. Downstream substrates and effectors of cPLA2α were screened via a phospho-antibody *** signaling pathways were identified by the functional annotation tool DAVID. Candidate proteins were verified using Western blot and colocalization was investigated via immunofluorescence. Western blot and immunohistochemistry were used to detect protein expression in HCC tissues. Prognosis evaluation was conducted using Kaplan-Meier and Cox-proportional hazards regression ***: Our findings showed that cPLA2α knockdown decreases cell-matrix adhesion but increases cell-cell adhesion in HepG2 cells. Microarray analysis revealed that phosphorylation of multiple proteins at specific sites were regulated by cPLA2α. These phosphorylated proteins were involved in various biological processes. In addition, our results indicated that the focal adhesion pathway was highly enriched in the cPLA2α-relevant signaling pathway. Furthermore, cPLA2α was found to elevate phosphorylation levels of FAK and paxillin, two crucial components of focal adhesion. Moreover, localization of p-FAK to focal adhesions in the plasma membrane was significantly reduced with the downregulation of cPLA2α. Clinically, cPLA2α expression was positively correlated with p-FAK levels. Additionally, high expression of both cPLA2α and p-FAK predicted the worst prognoses for HCC ***: Our study indicated that cPLA2α may promote cell-matrix adhesion via the FAK/paxillin pathway, which partly explains the malignant cPLA2α phenotype seen in HCC.