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
Citations
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References
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Journal ArticleDOI
Akt stimulates aerobic glycolysis in cancer cells
Rebecca Elstrom,Daniel E. Bauer,Monica Buzzai,Robyn Karnauskas,Marian H. Harris,David R. Plas,Hongming Zhuang,Ryan M. Cinalli,Abass Alavi,Charles M. Rudin,Craig B. Thompson +10 more
TL;DR: It is suggested that activation of the Akt oncogene is sufficient to stimulate the switch to aerobic glycolysis characteristic of cancer cells and that Akt activity renders cancer cells dependent on aerobic glyCOlysis for continued growth and survival.
Journal ArticleDOI
A transforming mutation in the pleckstrin homology domain of AKT1 in cancer
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TL;DR: The identification of a somatic mutation in human breast, colorectal and ovarian cancers that results in a glutamic acid to lysine substitution at amino acid 17 (E17K) in the lipid-binding pocket of AKT1 is reported.
Journal ArticleDOI
Sequence analysis of mutations and translocations across breast cancer subtypes
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TL;DR: Recurrent somatic mutations in PIK3CA, TP53, AKT1, GATA3 and MAP3K1 are confirmed and a recurrent MAGI3–AKT3 fusion enriched in triple-negative breast cancer lacking oestrogen and progesterone receptors and ERBB2 expression is identified.
Journal ArticleDOI
RB and cell cycle progression
TL;DR: It has been shown that Rb protein (pRb) is responsible for a major G1 checkpoint, blocking S-phase entry and cell growth.
Journal ArticleDOI
Role of Translocation in the Activation and Function of Protein Kinase B
Mirjana Andjelkovic,Dario R. Alessi,Roger Meier,Anne Fernandez,Ned J.C. Lamb,Matthias Frech,Peter Cron,Philip Cohen,John M. Lucocq,Brian A. Hemmings +9 more
TL;DR: The results indicate that PI3-K activity is required for translocation of PKB to the plasma membrane, where its activation occurs through phosphorylation of the same sites that are induced by insulin or IGF-1.