Cytosolic phospholipase A2α modulates cell-matrix adhesion <i>via</i> the FAK/paxillin pathway in hepatocellular carcinoma
<b>Objective</b> To explore the effect of cytosolic phospholipase A2α (cPLA2α) on hepatocellular carcinoma (HCC) cell adhesion and the underlying mechanisms.<b>Methods</b> Cell adhesion, detachment, and hanging-drop assays were utilized to examine the effect of cPLA2α on the...
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| Format: | Article |
| Language: | English |
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China Anti-Cancer Association
2019-06-01
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| Series: | Cancer Biology & Medicine |
| Subjects: | |
| Online Access: | http://www.cancerbiomed.org/index.php/cocr/article/view/1431 |
| _version_ | 1818200783777169408 |
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| author | Piao Guo Yuchao He Lu Chen Lisha Qi Dongming Liu Ziye Chen Manyu Xiao Liwei Chen Yi Luo Ning Zhang Hua Guo |
| author_facet | Piao Guo Yuchao He Lu Chen Lisha Qi Dongming Liu Ziye Chen Manyu Xiao Liwei Chen Yi Luo Ning Zhang Hua Guo |
| author_sort | Piao Guo |
| collection | DOAJ |
| description | <b>Objective</b> To explore the effect of cytosolic phospholipase A2α (cPLA2α) on hepatocellular carcinoma (HCC) cell adhesion and the underlying mechanisms.<b>Methods</b> 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 <i>via</i> a phospho-antibody microarray. Associated signaling pathways were identified by the functional annotation tool DAVID. Candidate proteins were verified using Western blot and colocalization was investigated <i>via</i> 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 analyses.<b>Results</b> 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 patients.<b>Conclusions</b> Our study indicated that cPLA2α may promote cell-matrix adhesion <i>via</i> the FAK/paxillin pathway, which partly explains the malignant cPLA2α phenotype seen in HCC. |
| first_indexed | 2024-12-12T02:43:09Z |
| format | Article |
| id | doaj.art-3cb20e9189924db1b33505fec1223f40 |
| institution | Directory Open Access Journal |
| issn | 2095-3941 2095-3941 |
| language | English |
| last_indexed | 2024-12-12T02:43:09Z |
| publishDate | 2019-06-01 |
| publisher | China Anti-Cancer Association |
| record_format | Article |
| series | Cancer Biology & Medicine |
| spelling | doaj.art-3cb20e9189924db1b33505fec1223f402022-12-22T00:41:07ZengChina Anti-Cancer AssociationCancer Biology & Medicine2095-39412095-39412019-06-0116237739010.20892/j.issn.2095-3941.2018.03862018000386Cytosolic phospholipase A2α modulates cell-matrix adhesion <i>via</i> the FAK/paxillin pathway in hepatocellular carcinomaPiao GuoYuchao HeLu Chen0Lisha Qi1Dongming Liu2Ziye Chen3Manyu Xiao4Liwei Chen5Yi Luo6Ning Zhang7Hua Guo8Department of Hepatobiliary CancerDepartment 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, ChinaDepartment of Hepatobiliary CancerDepartment of Tumor Cell BiologyDepartment of Tumor Cell BiologyDepartment of Tumor Cell BiologyDepartment of Tumor Cell BiologyDepartment of Tumor Cell BiologyDepartment of Tumor Cell Biology<b>Objective</b> To explore the effect of cytosolic phospholipase A2α (cPLA2α) on hepatocellular carcinoma (HCC) cell adhesion and the underlying mechanisms.<b>Methods</b> 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 <i>via</i> a phospho-antibody microarray. Associated signaling pathways were identified by the functional annotation tool DAVID. Candidate proteins were verified using Western blot and colocalization was investigated <i>via</i> 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 analyses.<b>Results</b> 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 patients.<b>Conclusions</b> Our study indicated that cPLA2α may promote cell-matrix adhesion <i>via</i> the FAK/paxillin pathway, which partly explains the malignant cPLA2α phenotype seen in HCC.http://www.cancerbiomed.org/index.php/cocr/article/view/1431Hepatocellular carcinomacytosolic phospholipase A2αcell-matrix adhesionFAKpaxillin |
| spellingShingle | Piao Guo Yuchao He Lu Chen Lisha Qi Dongming Liu Ziye Chen Manyu Xiao Liwei Chen Yi Luo Ning Zhang Hua Guo Cytosolic phospholipase A2α modulates cell-matrix adhesion <i>via</i> the FAK/paxillin pathway in hepatocellular carcinoma Cancer Biology & Medicine Hepatocellular carcinoma cytosolic phospholipase A2α cell-matrix adhesion FAK paxillin |
| title | Cytosolic phospholipase A2α modulates cell-matrix adhesion <i>via</i> the FAK/paxillin pathway in hepatocellular carcinoma |
| title_full | Cytosolic phospholipase A2α modulates cell-matrix adhesion <i>via</i> the FAK/paxillin pathway in hepatocellular carcinoma |
| title_fullStr | Cytosolic phospholipase A2α modulates cell-matrix adhesion <i>via</i> the FAK/paxillin pathway in hepatocellular carcinoma |
| title_full_unstemmed | Cytosolic phospholipase A2α modulates cell-matrix adhesion <i>via</i> the FAK/paxillin pathway in hepatocellular carcinoma |
| title_short | Cytosolic phospholipase A2α modulates cell-matrix adhesion <i>via</i> the FAK/paxillin pathway in hepatocellular carcinoma |
| title_sort | cytosolic phospholipase a2α modulates cell matrix adhesion i via i the fak paxillin pathway in hepatocellular carcinoma |
| topic | Hepatocellular carcinoma cytosolic phospholipase A2α cell-matrix adhesion FAK paxillin |
| url | http://www.cancerbiomed.org/index.php/cocr/article/view/1431 |
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