AKT isoform-specific expression and activation across cancer lineages

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

    Research output: Contribution to journalArticle

    6 Scopus citations

    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.

    Original languageEnglish (US)
    Article number742
    JournalBMC cancer
    Volume18
    Issue number1
    DOIs
    StatePublished - Jul 16 2018

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    Keywords

    • AKT
    • Activation
    • Expression
    • Isoform
    • Phosphorylation
    • RPPA

    ASJC Scopus subject areas

    • Genetics
    • Oncology
    • Cancer Research

    Cite this

    Wang, J., Zhao, W., Guo, H., Fang, Y., Stockman, S. E., Bai, S., Ng, P. K. S., Li, Y., Yu, Q., Lu, Y., Jeong, K. J., Chen, X., Gao, M., Liang, J., Li, W., Tian, X., Jonasch, E., Mills, G. B., & Ding, Z. (2018). AKT isoform-specific expression and activation across cancer lineages. BMC cancer, 18(1), [742]. https://doi.org/10.1186/s12885-018-4654-5