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Open AccessJournal ArticleDOI

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.

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Beyond Proteolysis-Targeting Chimeric Molecules: Designing Heterobifunctional Molecules Based on Functional Effectors.

TL;DR: Heterobifunctional molecules other than PROTACs are introduced, the limitations of existing molecules are summarized, the main challenges are listed, and perspectives for future research directions are proposed, providing insight into alternative design strategies based on substrate-proximity-based targeting.
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The PI3K/AKT signaling pathway in cancer: Molecular mechanisms and possible therapeutic interventions.

TL;DR: In this paper , a review of the relationship between PI3K/AKT signaling pathway and factors contributing to initiation and development of various cancers is presented, and therapeutic interventions regulating this signaling pathway have been summarized.
Journal ArticleDOI

Role of protein phosphorylation in cell signaling, disease, and the intervention therapy

TL;DR: In this article , the authors analyzed 303 small-molecule protein phosphorylation kinase inhibitors (PKIs) registered and participated in clinical research obtained in a database named Protein Kinase Inhibitor Database (PKIDB), including 68 drugs approved by the Food and Drug Administration of the United States.
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AKT Serine/Threonine Kinase 2-mediated phosphorylation of Fascin Threonine 403 regulates esophageal cancer progression.

TL;DR: In this article , a novel phosphorylation of Fascin Threonine 403 (Fascin-T403) mediated by AKT serine/threonine kinase 2 (AKT2) was studied using mass spectrometry data from esophageal cancer tissues (iProX database: IPX0002501000).
Journal ArticleDOI

Mir-29b in Breast Cancer: A Promising Target for Therapeutic Approaches

TL;DR: Of particular interest are the data showing that miR-29b1-5p counteracts cell proliferation and migration and reduces stemness in breast tumor cells with a triple negative phenotype, and its possible implication in phenotype-specific management of breast tumors.
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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PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest.

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.
Journal ArticleDOI

Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas.

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.
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