Journal
CELL RESEARCH
Volume 24, Issue 2, Pages 204-217Publisher
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/cr.2013.158
Keywords
copy number alterations; MPZL1; cortactin; migration; hepatocellular carcinoma
Categories
Funding
- National Key Basic Research Program of China [2013CB910500]
- National Natural Science Foundation of China [81125016, 81071637, 91029728]
- Shanghai Science and Technology Commission [11XD1404500]
- Shanghai Municipal Education Commission and Shanghai Municipal Health Bureau [11SG18, XBR2011039]
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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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