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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.
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

Akt/PKB: one kinase, many modifications

TL;DR: An overview of the different post-translational modifications identified for Akt, focusing on their consequences for this kinase activity, is provided.
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Protein phosphatase 2A is the main phosphatase involved in the regulation of protein kinase B in rat adipocytes

TL;DR: PP2A is the principal phosphatase that dephosphorylates PKB in adipocytes, and PP2A subunits were found in several subcellular compartments, including plasma membranes where the phosphorylation of PKB is thought to occur.
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Expression of constitutively activated Akt in the mammary gland leads to excess lipid synthesis during pregnancy and lactation.

TL;DR: Transduction of the CIT3 mammary epithelial cell line with a recombinant human adenovirus encoding myr-Akt resulted in an increase in glucose transport and lipid biosynthesis, suggesting that Akt plays an important role in regulation of lipid metabolism.
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Regulation of Akt signaling activation by ubiquitination.

TL;DR: This work has shown that the cancer-associated Akt mutant recently identified in a subset of human cancers displays enhanced Akt ubiquitination, in turn contributing to Akt hyperactivation, suggesting a potential role of Akt Ubiquitination in cancers.
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Targeting Akt3 Signaling in Triple-Negative Breast Cancer

TL;DR: The results imply that Akt3 has a specific function in TNBCs; thus, its therapeutic targeting may provide a new treatment option for this tumor subtype.
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