Open AccessAP 4 positively regulates LAPTM 4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity
Author(s) -
Meng Yue,
Wang Lu,
Xu Jianjun,
Zhang Qingyun
Publication year - 2018
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12171
Subject(s) - metastasis , hepatocellular carcinoma , promoter , cancer research , transcription factor , biology , gene , transcription (linguistics) , cell growth , microbiology and biotechnology , gene expression , cancer , genetics , linguistics , philosophy
Polymorphisms of the lysosomal‐associated protein transmembrane‐4 beta ( LAPTM 4B) gene are related to various forms of tumour susceptibility, which led us to hypothesize that some unique transcription factors targeting this polymorphism region may affect the biological function of LAPTM 4B in tumour progression. In this study, we found that the transcription factor AP 4 directly binds to the polymorphism region of the LAPTM 4B gene promoter and induces its transcription. In addition, we demonstrated that AP 4 promotes hepatocellular carcinoma (HCC) cell proliferation and metastasis and depresses chemotherapy sensitivity via LAPTM 4B by activating the PI 3K/ AKT signalling pathway and caspase‐dependent pathway. Interestingly, we found that AP 4 could not only regulate LAPTM 4B by directly binding to the promoter, but also be regulated via a positive feedback mechanism involving LAPTM 4B acting on c‐myc. Finally, we showed that AP 4 and LAPTM 4B are highly coexpressed in HCC tissues, and their coexpression may be a marker of poor prognosis. These findings provide evidence of the expression and functional coupling between AP 4 and LAPTM 4B and shed light on the regulation of LAPTM 4B and its function in liver cancer.