AKT isoform-specific expression and activation across cancer lineages
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 particu...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-07-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-018-4654-5 |
| _version_ | 1819070992714039296 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jue Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T17:14:45Z |
| format | Article |
| id | doaj.art-9749cf56d10842c794d00f85219d164d |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-21T17:14:45Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-9749cf56d10842c794d00f85219d164d2022-12-21T18:56:19ZengBMCBMC Cancer1471-24072018-07-0118111010.1186/s12885-018-4654-5AKT isoform-specific expression and activation across cancer lineagesJue Wang0Wei Zhao1Huifang Guo2Yong Fang3Sarah Elizabeth Stockman4Shanshan Bai5Patrick Kwok-Shing Ng6Yang Li7Qinghua Yu8Yiling Lu9Kang Jin Jeong10Xiaohua Chen11Meng Gao12Jiyong Liang13Wentao Li14Xingsong Tian15Eric Jonasch16Gordon B. Mills17Zhiyong Ding18Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong UniversityDepartment of Systems Biology, The University of Texas MD Anderson Cancer CenterDepartment of Systems Biology, The University of Texas MD Anderson Cancer CenterDepartment of Systems Biology, The University of Texas MD Anderson Cancer CenterDepartment of Systems Biology, The University of Texas MD Anderson Cancer CenterGenitourinary Medical Oncology, The University of Texas MD Anderson Cancer CenterInstitute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer CenterDepartment of Systems Biology, The University of Texas MD Anderson Cancer CenterDepartment of Systems Biology, The University of Texas MD Anderson Cancer CenterDepartment of Systems Biology, The University of Texas MD Anderson Cancer CenterDepartment of Systems Biology, The University of Texas MD Anderson Cancer CenterDepartment of Systems Biology, The University of Texas MD Anderson Cancer CenterDepartment of Systems Biology, The University of Texas MD Anderson Cancer CenterDepartment of Systems Biology, The University of Texas MD Anderson Cancer CenterDepartment of Interventional Radiology, Cancer Hospital, Fudan UniversityDepartment of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong UniversityGenitourinary Medical Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Systems Biology, The University of Texas MD Anderson Cancer CenterDepartment of Systems Biology, The University of Texas MD Anderson Cancer CenterAbstract 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.http://link.springer.com/article/10.1186/s12885-018-4654-5AKTIsoformExpressionPhosphorylationActivationRPPA |
| spellingShingle | 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 AKT isoform-specific expression and activation across cancer lineages BMC Cancer AKT Isoform Expression Phosphorylation Activation RPPA |
| title | AKT isoform-specific expression and activation across cancer lineages |
| title_full | AKT isoform-specific expression and activation across cancer lineages |
| title_fullStr | AKT isoform-specific expression and activation across cancer lineages |
| title_full_unstemmed | AKT isoform-specific expression and activation across cancer lineages |
| title_short | AKT isoform-specific expression and activation across cancer lineages |
| title_sort | akt isoform specific expression and activation across cancer lineages |
| topic | AKT Isoform Expression Phosphorylation Activation RPPA |
| url | http://link.springer.com/article/10.1186/s12885-018-4654-5 |
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