title: SERPINA5 inhibits tumor cell migration by modulating the fibronectin-integrin β1 signaling pathway in hepatocellular carcinoma.
abstract: In our previous study, we identified 1241 loci with somatic copy number alterations in human hepatocellular carcinoma (HCC) using Affymetrix SNP 6.0 arrays, and a putative cancer gene SERPINA5 was uncovered in a novel chromosomal region with recurrent copy number loss at 14q31.1-32.13. The SERPINA5 was reported to be deregulated in renal, breast, prostate and ovarian cancers. However, the roles of SERPINA5 in cancer remain greatly elusive. In this study, we found that the DNA dosage and expression level of the SERPINA5 gene were significantly decreased in HCC by quantitative real-time PCR. Notably, the expression levels of SERPINA5 negatively correlated with malignant progression of HCC. The SERPINA5 gene was further observed to reduce in vitro and in vivo metastatic potential of HCC cells. Moreover, secreted SERPINA5 protein also could inhibit the metastatic ability of HCC cells. Finally, we discovered that one of the mechanisms explaining SERPINA5 inhibition of HCC metastasis is through direct interaction with fibronectin and disruption of the fibronectin-integrin signaling pathway. These findings highlight an important role of SERPINA5 in the regulation of migratory and metastatic potentials of HCC and suggest a potential application of SERPINA5 in cancer treatment.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jing
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Deshui
authors.initials: D
authors.lastname: Jia
authors.affiliation: State Key Laboratory for Liver Research, Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Wong
authors.affiliation: State Key Laboratory for Liver Research, Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Irene Oi-Lin
authors.initials: IO
authors.lastname: Ng
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Fangyu
authors.initials: F
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: xz_wu@shmu.edu.cn.
authors.forename: Xingzhong
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: xhhe@shsci.org.
authors.forename: Xianghuo
authors.initials: X
authors.lastname: He
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D018046:Protein C Inhibitor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D005353:Fibronectins; D019012:Integrin beta1; D009363:Neoplasm Proteins; D018046:Protein C Inhibitor; C534934:SERPINA5 protein, human
keywords: Hepatocellular carcinoma; Metastasis; Migration; SERPINA5