Amplification of MPZL1/PZR promotes tumor cell migration through Src-mediated phosphorylation of cortactin in hepatocellular carcinoma |
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| Authors: | Deshui Jia Ying Jing Zhenfeng Zhang Li Liu Jie Ding Fangyu Zhao Chao Ge Qifeng Wang Taoyang Chen Ming Yao Jinjun Li Jianren Gu Xianghuo He |
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| Institution: | 1.State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China;2.Shanghai Medical College, Fudan University, Shanghai 200032, China;3.Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, China;4.Qidong Liver Cancer Institute, Qidong, Jiangsu 226200, China |
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| Abstract: | We have previously identified 1 241 regions of somatic copy number alterations (CNAs) in hepatocellular carcinoma (HCC). In the present study, we found that a novel recurrent focal amplicon, 1q24.1-24.2, targets the MPZL1 gene in HCC. Notably, there is a positive correlation between the expression levels of MPZL1 and intrahepatic metastasis of the HCC specimens. MPZL1 can significantly enhance the migratory and metastatic potential of the HCC cells. Moreover, we found that one of the mechanisms by which MPZL1 promotes HCC cell migration is by inducing the phosphorylation and activation of the pro-metastatic protein, cortactin. Additionally, we found that Src kinase mediates the phosphorylation and activation of cortactin induced by MPZL1 overexpression. Taken together, these findings suggest that MPZL1 is a novel pro-metastatic gene targeted by a recurrent region of copy number amplification at 1q24.1-24.2 in HCC. |
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| Keywords: | copy number alterations MPZL1 cortactin migration hepatocellular carcinoma |
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