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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2016 | Research

The E545K mutation of PIK3CA promotes gallbladder carcinoma progression through enhanced binding to EGFR

Authors: Shuai Zhao, Yang Cao, Shi-bo Liu, Xu-an Wang, Run-fa Bao, Yi-jun Shu, Yun-ping Hu, Yi-jian Zhang, Lin Jiang, Fei Zhang, Hai-bin Liang, Huai-feng Li, Qiang Ma, Yi Xu, Zheng Wang, Yi-chi Zhang, Lei Chen, Jian Zhou, Ying-bin Liu

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2016

Abstract

Background

Gallbladder carcinoma (GBC) is the most common malignancy of the bile duct and patients with GBC have extremely poor prognoses. PIK3CA, which encodes the phosphoinositide 3-kinase (PI3K) subunit p110α, is frequently mutated in many cancers, including GBC. The function of the E545K mutation in GBC is not fully understood.

Methods

E545K mutation was determined in human GBC tissues by targeted sequencing. The effects of E545K mutation and PI3K selective inhibitor, A66 on GBC cells were evaluated using Cell Counting Kit-8 (CCK-8) cell Viability and transwell assays. The mechanisms of E545K mutation and A66 were analyzed by western blot and co-immunoprecipitation (Co-IP) assay. Subcutaneous xenograft models in nude mice were employed to evaluate the role of E545K mutation and A66 in GBC progression.

Results

The rate of PIK3CA E545K mutation in GBC patients was 6.15 %. And the survival of GBC patients was correlated with E545K mutation significantly (P < 0.05). The E545K mutation promoted proliferation, migration and invasion of GBC cells in vitro and tumor proliferation in vivo. A66 suppressed proliferation of GBC cells in vitro and tumor proliferation in vivo.

Conclusion

The prognoses of patients with E545K mutation were worse than patients without this mutation. The E545K mutation promoted GBC progression through enhanced binding to EGFR and activating downstream akt activity. The PI3K selective inhibitor, A66, suppressed gallbladder carcinoma proliferation.

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Title: The E545K mutation of PIK3CA promotes gallbladder carcinoma progression through enhanced binding to EGFR
Authors: Shuai Zhao
Yang Cao
Shi-bo Liu
Xu-an Wang
Run-fa Bao
Yi-jun Shu
Yun-ping Hu
Yi-jian Zhang
Lin Jiang
Fei Zhang
Hai-bin Liang
Huai-feng Li
Qiang Ma
Yi Xu
Zheng Wang
Yi-chi Zhang
Lei Chen
Jian Zhou
Ying-bin Liu
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2016
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-016-0370-7

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Abstract

Background

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Conclusion

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