Akt Isoforms: A Family Affair in Breast Cancer
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TLDR
In this article, the authors analyzed current literatures on distinct functions of Akt isoforms in breast cancer and proposed an approach to target the Akt signaling pathway for cancer therapy, which is critical to effectively target this pathway.Abstract:
Akt, also known as protein kinase B (PKB), belongs to the AGC family of protein kinases. It acts downstream of the phosphatidylinositol 3-kinase (PI3K) and regulates diverse cellular processes, including cell proliferation, cell survival, metabolism, tumor growth and metastasis. The PI3K/Akt signaling pathway is frequently deregulated in breast cancer and plays an important role in the development and progression of breast cancer. There are three closely related members in the Akt family, namely Akt1(PKBα), Akt2(PKBβ) and Akt3(PKBγ). Although Akt isoforms share similar structures, they exhibit redundant, distinct as well as opposite functions. While the Akt signaling pathway is an important target for cancer therapy, an understanding of the isoform-specific function of Akt is critical to effectively target this pathway. However, our perception regarding how Akt isoforms contribute to the genesis and progression of breast cancer changes as we gain new knowledge. The purpose of this review article is to analyze current literatures on distinct functions of Akt isoforms in breast cancer.read more
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References
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Journal ArticleDOI
AKT/PKB and Other D3 Phosphoinositide-Regulated Kinases: Kinase Activation by Phosphoinositide-Dependent Phosphorylation
TL;DR: The current understanding of the regulation and function of the Akt kinase is presented and the common and unique features of the activation processes of Akt and the AGC and Tec kinase families are discussed.
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An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer.
Katherine Stemke-Hale,Ana M. Gonzalez-Angulo,Ana Lluch,Richard M. Neve,Wen Lin Kuo,Michael Davies,Mark S. Carey,Zhi Hu,Yinghui Guan,Aysegul A. Sahin,W. Fraser Symmans,Lajos Pusztai,Laura K. Nolden,Hugo M. Horlings,Katrien Berns,Mien Chie Hung,Marc J. van de Vijver,Vicente Valero,Joe W. Gray,René Bernards,Gordon B. Mills,Bryan T. Hennessy +21 more
TL;DR: PI3K pathway aberrations likely play a distinct role in the pathogenesis of different breast cancer subtypes and the specific aberration present may have implications for the selection of PI3K-targeted therapies in hormone receptor-positive breast cancer.
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PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest.
Jiyong Liang,Judit Zubovitz,Teresa Petrocelli,Rouslan Kotchetkov,Michael K. Connor,Kathy Han,Jin hwa Lee,Sandra Ciarallo,Charles Catzavelos,Richard G. Beniston,Edmee Franssen,Joyce M. Slingerland +11 more
TL;DR: It is shown that activation of protein kinase B (PKB)/Akt, contributes to resistance to antiproliferative signals and breast cancer progression in part by impairing the nuclear import and action of p27.
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Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas.
Alfonso Bellacosa,D. De Feo,Andrew K. Godwin,Daphne W. Bell,Jin Quan Cheng,Deborah A. Altomare,Minghong Wan,Louis Dubeau,Giovanni Scambia,Valeria Masciullo,Gabriella Ferrandina,P. Benedetti Panici,Salvatore Mancuso,Giovanni Neri,Joseph R. Testa +14 more
TL;DR: The difference in the incidence of AKT2 alterations in ovarian and breast cancer suggests a specific role for this gene in ovarian oncogenesis and a significant association was found betweenAKT2 amplification and amplification of the proto‐oncogenes MYC and ERBB2, suggesting that amplification of AKt2 defines an independent subset of breast and ovarian cancers.
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PHLPP: A Phosphatase that Directly Dephosphorylates Akt, Promotes Apoptosis, and Suppresses Tumor Growth
TL;DR: PHLPP levels are markedly reduced in several colon cancer and glioblastoma cell lines that have elevated Akt phosphorylation, consistent with PHLPP terminating Akt signaling by directly dephosphorylating and inactivating Akt.