An integrin beta4-EGFR unit promotes hepatocellular carcinoma lung metastases by enhancing anchorage independence through activation of FAK–AKT pathway

• Published in: Cancer letters Vol. 376; no. 1; pp. 188 - 196
• Main Authors: Leng, Chao, Zhang, Zhan-guo, Chen, Wei-xun, Luo, Hong-ping, Song, Jia, Dong, Wei, Zhu, Xuan-ru, Chen, Xiao-ping, Liang, Hui-fang, Zhang, Bi-xiang
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 28.06.2016; Elsevier Limited
• Subjects: Adult; Aged; Animals; Anoikis; Carcinoma, Hepatocellular - enzymology; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - secondary; Cell culture; Cell Proliferation; Cloning; Conflicts of interest; EGFR; Enzyme Activation; Female; Focal Adhesion Kinase 1 - metabolism; Gene Expression Regulation, Neoplastic; Hematology, Oncology and Palliative Medicine; Hep G2 Cells; Hepatocellular carcinoma; Heterografts; Hospitals; Humans; Immunoglobulins; Integrin beta4; Integrin beta4 - genetics; Integrin beta4 - metabolism; Kinases; Laboratory animals; Liver cancer; Liver Neoplasms - enzymology; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Lung Neoplasms - enzymology; Lung Neoplasms - genetics; Lung Neoplasms - secondary; Male; Medical prognosis; Metastases; Metastasis; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Neoplasm Transplantation; Plasmids; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Receptor, Epidermal Growth Factor - metabolism; RNA Interference; Rodents; Signal Transduction; Transfection; Tumor Burden; China; ITGB4; adjacent nontumorous liver tissue; sodium dodecyl sulfate polyacrylamide gel electrophoresis; Hepatocellular carcinoma; co-immunoprecipitation; phosphate-buffered saline; doxycycline; EGFR; Metastases; protein kinase B; hematoxylin and eosin; PBS; epithelial–mesenchymal transition; H&E; PKB; epidermal growth factor receptor; Integrin beta4; HCC; ANLT; Co-IP; Dox; SDS–PAGE; EMT; FAK; focal adhesion kinase; Anoikis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2016.03.023

Highlights • Overexpression of ITGB4 is found in HCC tissues and aggressive HCC cell lines and associated with malignant clinic-pathological features. • ITGB4 interacts with EGFR in a ligand independent manner to promote anchorage independence by activating AKT signaling pathway. • The ITGB4–EGFR unit triggers the FAK rather than SRC to activate AKT pathway. • ITGB4 enhances tumor growth and pulmonary metastases of HCC in vivo.