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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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Journal ArticleDOI

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.
Journal ArticleDOI

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.
Journal ArticleDOI

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

Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling.

TL;DR: It is reported that knocking down the expression of inositol polyphosphate 4-phosphatase type II in human epithelial cells, like knockdown of PTEN, resulted in enhanced Akt activation and anchorage-independent growth and enhanced overall motility, suggesting that INPP4B is a tumor suppressor.
Journal ArticleDOI

Akt blocks breast cancer cell motility and invasion through the transcription factor NFAT.

TL;DR: Results indicate that while Akt can promote tumor progression through increased cell survival mechanisms, it can block breast cancer cell motility and invasion by a mechanism that depends, at least in part, on the NFAT transcription factor.
Journal ArticleDOI

PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP.

TL;DR: The data indicate that activation of SREBP by Akt leads to the induction of key enzymes of the cholesterol and fatty acid biosynthesis pathways, and thus membrane lipid biosynthesis.
Journal ArticleDOI

PKBα/Akt1 Acts Downstream of DNA-PK in the DNA Double-Strand Break Response and Promotes Survival

TL;DR: This work reports a route by which activated PKB promotes survival in response to DNA insults in vivo, and places PKB downstream of DNA-PK in the DNA damage response signaling cascade, where it provides a prosurvival signal.
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