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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

AKT isoform-specific expression and activation across cancer lineages

Authors: Jue Wang, Wei Zhao, Huifang Guo, Yong Fang, Sarah Elizabeth Stockman, Shanshan Bai, Patrick Kwok-Shing Ng, Yang Li, Qinghua Yu, Yiling Lu, Kang Jin Jeong, Xiaohua Chen, Meng Gao, Jiyong Liang, Wentao Li, Xingsong Tian, Eric Jonasch, Gordon B. Mills, Zhiyong Ding

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Aberrant AKT activation is prevalent across human cancer lineages, providing an important therapeutic target. AKT comprises three isoforms that mediate critical non-redundant, even opposing functions in cancer pathophysiology. Therefore, targeting specific AKT isoforms in particular cancers may be more effective than pan-AKT inhibition while avoiding disadvantages of pan-AKT inhibition. Currently, AKT isoform-specific expression and activation in cancer are not clearly characterized.

Methods

We systematically characterized AKT isoform-specific expression and activation in 211 cancer cell lines derived from different lineages and genetic backgrounds using a reverse-phase protein array platform.

Results

We found that phosphorylation, but not expression, of AKT1 and AKT2 was coordinated in most but not all cells. Different cancer lineages displayed differential AKT1 and AKT2 expression and phosphorylation. A PIK3CA hotspot mutation H1047R but not E545K was associated with selective activation of AKT2 but not AKT1.

Conclusions

Our study identified and validated AKT isoform-specific expression and phosphorylation in certain cell lines and demonstrated that genetic changes can affect AKT isoform-specific activation. These results provide a more precise understanding of AKT isoform-specific signaling and, in addition, facilitate AKT isoform targeting for personalized cancer therapies.
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Metadata
Title
AKT isoform-specific expression and activation across cancer lineages
Authors
Jue Wang
Wei Zhao
Huifang Guo
Yong Fang
Sarah Elizabeth Stockman
Shanshan Bai
Patrick Kwok-Shing Ng
Yang Li
Qinghua Yu
Yiling Lu
Kang Jin Jeong
Xiaohua Chen
Meng Gao
Jiyong Liang
Wentao Li
Xingsong Tian
Eric Jonasch
Gordon B. Mills
Zhiyong Ding
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4654-5

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