AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity
Polymorphisms of the lysosomal‐associated protein transmembrane‐4 beta (LAPTM4B) 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 LAPTM4B in tumour p...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2018-03-01
|
Series: | Molecular Oncology |
Subjects: | |
Online Access: | https://doi.org/10.1002/1878-0261.12171 |
id |
doaj-3d4891eefe694b3fab3236e9244a27ad |
---|---|
record_format |
Article |
spelling |
doaj-3d4891eefe694b3fab3236e9244a27ad2020-11-25T03:49:33ZengWileyMolecular Oncology1574-78911878-02612018-03-0112337339010.1002/1878-0261.12171AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivityYue Meng0Lu Wang1Jianjun Xu2Qingyun Zhang3Department of Clinical Laboratory Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital & Institute Beijing ChinaDepartment of Clinical Laboratory Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital & Institute Beijing ChinaDepartment of Clinical Laboratory Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital & Institute Beijing ChinaDepartment of Clinical Laboratory Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital & Institute Beijing ChinaPolymorphisms of the lysosomal‐associated protein transmembrane‐4 beta (LAPTM4B) 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 LAPTM4B in tumour progression. In this study, we found that the transcription factor AP4 directly binds to the polymorphism region of the LAPTM4B gene promoter and induces its transcription. In addition, we demonstrated that AP4 promotes hepatocellular carcinoma (HCC) cell proliferation and metastasis and depresses chemotherapy sensitivity via LAPTM4B by activating the PI3K/AKT signalling pathway and caspase‐dependent pathway. Interestingly, we found that AP4 could not only regulate LAPTM4B by directly binding to the promoter, but also be regulated via a positive feedback mechanism involving LAPTM4B acting on c‐myc. Finally, we showed that AP4 and LAPTM4B 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 AP4 and LAPTM4B and shed light on the regulation of LAPTM4B and its function in liver cancer.https://doi.org/10.1002/1878-0261.12171AP4C‐MYChepatocellular carcinomaLAPTM4Btranscription |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yue Meng Lu Wang Jianjun Xu Qingyun Zhang |
spellingShingle |
Yue Meng Lu Wang Jianjun Xu Qingyun Zhang AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity Molecular Oncology AP4 C‐MYC hepatocellular carcinoma LAPTM4B transcription |
author_facet |
Yue Meng Lu Wang Jianjun Xu Qingyun Zhang |
author_sort |
Yue Meng |
title |
AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity |
title_short |
AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity |
title_full |
AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity |
title_fullStr |
AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity |
title_full_unstemmed |
AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity |
title_sort |
ap4 positively regulates laptm4b to promote hepatocellular carcinoma growth and metastasis, while reducing chemotherapy sensitivity |
publisher |
Wiley |
series |
Molecular Oncology |
issn |
1574-7891 1878-0261 |
publishDate |
2018-03-01 |
description |
Polymorphisms of the lysosomal‐associated protein transmembrane‐4 beta (LAPTM4B) 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 LAPTM4B in tumour progression. In this study, we found that the transcription factor AP4 directly binds to the polymorphism region of the LAPTM4B gene promoter and induces its transcription. In addition, we demonstrated that AP4 promotes hepatocellular carcinoma (HCC) cell proliferation and metastasis and depresses chemotherapy sensitivity via LAPTM4B by activating the PI3K/AKT signalling pathway and caspase‐dependent pathway. Interestingly, we found that AP4 could not only regulate LAPTM4B by directly binding to the promoter, but also be regulated via a positive feedback mechanism involving LAPTM4B acting on c‐myc. Finally, we showed that AP4 and LAPTM4B 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 AP4 and LAPTM4B and shed light on the regulation of LAPTM4B and its function in liver cancer. |
topic |
AP4 C‐MYC hepatocellular carcinoma LAPTM4B transcription |
url |
https://doi.org/10.1002/1878-0261.12171 |
work_keys_str_mv |
AT yuemeng ap4positivelyregulateslaptm4btopromotehepatocellularcarcinomagrowthandmetastasiswhilereducingchemotherapysensitivity AT luwang ap4positivelyregulateslaptm4btopromotehepatocellularcarcinomagrowthandmetastasiswhilereducingchemotherapysensitivity AT jianjunxu ap4positivelyregulateslaptm4btopromotehepatocellularcarcinomagrowthandmetastasiswhilereducingchemotherapysensitivity AT qingyunzhang ap4positivelyregulateslaptm4btopromotehepatocellularcarcinomagrowthandmetastasiswhilereducingchemotherapysensitivity |
_version_ |
1724494929796792320 |