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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

Distinct Akt phosphorylation states are required for insulin regulated Glut4 and Glut1-mediated glucose uptake

TL;DR: In this article, it was shown that an intact hydrophobic motif domain is required for Glut4-mediated glucose uptake, whereas Glut1-dependent glucose uptake also requires mTORC2 phosphorylation of the HM domain.
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ATM protein kinase mediates full activation of Akt and regulates glucose transporter 4 translocation by insulin in muscle cells.

TL;DR: To investigate the function of ATM in insulin signal transduction, insulin resistance was induced in rats by feeding them a high-fat diet and decreased ATM expression suggests that ATM is involved in the development of insulin resistance through down-regulation of Akt activity.
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Reduced Expression of PTEN Protein and Its Prognostic Implications in Invasive Ductal Carcinoma of the Breast

TL;DR: The inactivation ofPTEN, demonstrated by a reduced expression of PTEN protein by immunohistochemistry, was found in about one third of all breast cancers, and the reduced expression correlated with lymph node metastases and a worse prognosis in the patients with breast cancer.
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Twist-mediated Epithelial-mesenchymal Transition Promotes Breast Tumor Cell Invasion via Inhibition of Hippo Pathway

TL;DR: It is reported that Twist overexpression increased expression of PAR1, an upstream regulator of the Hippo pathway; PAR1 promotes invasion, migration, and CSC-like properties in breast cancer by activating the transcriptional co-activator TAZ.
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