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

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

doi:10.1038/cr.2013.158

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

Cell Res. 2014 Feb;24(2):204-17. doi: 10.1038/cr.2013.158. Epub 2013 Dec 3.

Authors

Deshui Jia¹, Ying Jing¹, Zhenfeng Zhang², Li Liu², Jie Ding², Fangyu Zhao², Chao Ge², Qifeng Wang³, Taoyang Chen⁴, Ming Yao², Jinjun Li², Jianren Gu², Xianghuo He²

Affiliations

¹ 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.
² State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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
Phosphoproteins / antagonists & inhibitors
Phosphoproteins / genetics
Phosphoproteins / metabolism*
Phosphorylation
Protein Isoforms / antagonists & inhibitors
Protein Isoforms / genetics
Protein Isoforms / metabolism
RNA Interference
RNA, Small Interfering
Transplantation, Heterologous
src-Family Kinases / antagonists & inhibitors
src-Family Kinases / metabolism*

Substances

CTTN protein, human
Cortactin
Intracellular Signaling Peptides and Proteins
MPZL1 protein, human
Phosphoproteins
Protein Isoforms
RNA, Small Interfering
src-Family Kinases