CD31 regulates metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma via the ITGB1-FAK-Akt signaling pathway

Yuan-Yuan Zhang; Ling-Qun Kong; Xiao-Dong Zhu; Hao Cai; Cheng-Hao Wang; Wen-Kai Shi; Man-Qing Cao; Xiao-Long Li; Kang-Shuai Li; Shi-Zhe Zhang; Zong-Tao Chai; Jian-Yang Ao; Bo-Gen Ye; Hui-Chuan Sun

doi:10.1016/j.canlet.2018.05.004

CD31 regulates metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma via the ITGB1-FAK-Akt signaling pathway

Cancer Lett. 2018 Aug 10:429:29-40. doi: 10.1016/j.canlet.2018.05.004. Epub 2018 May 8.

Authors

Affiliations

¹ Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, The Key Laboratory for Carcinogenesis and Cancer Invasion, The Ministry of Education of China, Shanghai, 200032, China.
² Department of Hepatobiliary Surgery, Binzhou Medical College Affiliated Hospital, Binzhou, Shandong, 256603, China.
³ Department of Liver Surgery, Fudan University Cancer Center, Cancer Hospital, Shanghai, 200032, China.
⁴ Department of Hepatobiliary Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, 200438, China.
⁵ Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
⁶ Department of Hepatobiliary Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
⁷ Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, The Key Laboratory for Carcinogenesis and Cancer Invasion, The Ministry of Education of China, Shanghai, 200032, China. Electronic address: [email protected].

PMID: 29746931
DOI: 10.1016/j.canlet.2018.05.004

Abstract

Platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31) is a well-known marker of endothelial cells and a key factor for adhesion and accumulation of platelets. CD31 plays roles in cell proliferation, apoptosis, migration, and cellular immunity. CD31 is also expressed on tumor cells, such as breast cancer cells and non-Hodgkin's lymphomas, and contributes to tumor cell invasion. Here, our experiments show that CD31 promotes metastasis by inducing the epithelial-mesenchymal transition in hepatocellular carcinoma by up-regulating integrin β1 via the FAK/Akt signaling pathway.

Keywords: CD31; Epithelial–mesenchymal transition; Hepatocellular carcinoma; Integrin β1; PECAM-1.

Publication types

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

MeSH terms

Adaptor Proteins, Signal Transducing
Animals
Carcinoma, Hepatocellular / drug therapy*
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism
Cell Line, Tumor
Cycloheximide / pharmacology*
Epithelial-Mesenchymal Transition / drug effects*
Epithelial-Mesenchymal Transition / genetics
Focal Adhesion Kinase 1 / metabolism
Hep G2 Cells
Humans
Intracellular Signaling Peptides and Proteins / metabolism
Liver Neoplasms / drug therapy*
Liver Neoplasms / genetics
Liver Neoplasms / metabolism
Male
Membrane Proteins / metabolism
Mice, Inbred BALB C
Mice, Nude
Neoplasm Metastasis
Platelet Endothelial Cell Adhesion Molecule-1 / genetics
Platelet Endothelial Cell Adhesion Molecule-1 / metabolism*
Protein Synthesis Inhibitors / pharmacology
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction / drug effects
Signal Transduction / genetics
Xenograft Model Antitumor Assays / methods*

Substances

Adaptor Proteins, Signal Transducing
ITGB1BP1 protein, human
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Platelet Endothelial Cell Adhesion Molecule-1
Protein Synthesis Inhibitors
Cycloheximide
Focal Adhesion Kinase 1
PTK2 protein, human
Proto-Oncogene Proteins c-akt