Amplification of MPZL1/PZR promotes tumor cell migration through Src-mediated phosphorylation of cortactin in hepatocellular carcinoma

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, lq24.1-24.2, targets the MPZL1 gene in HCC. Notably, there is a positive correlation between the expression l...

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Bibliographic Details
Published in:Cell research 2014-02, Vol.24 (2), p.204-217
Main Authors: Jia, Deshui, Jing, Ying, Zhang, Zhenfeng, Liu, Li, Ding, Jie, Zhao, Fangyu, Ge, Chao, Wang, Qifeng, Chen, Taoyang, Yao, Ming, Li, Jinjun, Gu, Jianren, He, Xianghuo
Format: Article
Language:English
Subjects:
Animals
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Cell Line, Tumor
Chromosomes, Human, Pair 1
Cortactin - metabolism
DNA Copy Number Variations
Down-Regulation
Hep G2 Cells
Humans
Intracellular Signaling Peptides and Proteins - antagonists & inhibitors
Intracellular Signaling Peptides and Proteins - genetics
Intracellular Signaling Peptides and Proteins - metabolism
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Lung Neoplasms - pathology
Lung Neoplasms - secondary
Mice
Mice, Nude
Original
Phosphoproteins - antagonists & inhibitors
Phosphoproteins - genetics
Phosphoproteins - metabolism
Phosphorylation
Protein Isoforms - antagonists & inhibitors
Protein Isoforms - genetics
Protein Isoforms - metabolism
RNA Interference
RNA, Small Interfering
src-Family Kinases - antagonists & inhibitors
src-Family Kinases - metabolism
Transplantation, Heterologous
介导
化促
皮层
磷酸化
细胞迁移
肝癌细胞
肿瘤细胞
蛋白激酶
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Summary: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, lq24.1-24.2, 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 lq24.1-24.2 in HCC.
ISSN:1001-0602
1748-7838
DOI:10.1038/cr.2013.158