Cooperative activation of PDK1 and AKT by MAPK4 enhances cancer growth and resistance to therapy

Article Multidisciplinary Sciences

A COP1-GATA2 axis suppresses AR signaling and prostate cancer

Tao Shen et al.

Summary: GATA2 degradation driven by COP1 is a direct mechanism for regulating AR expression and activation, PCa growth, and castration resistance.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

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Article Medicine, Research & Experimental

MAPK4 promotes prostate cancer by concerted activation of androgen receptor and AKT

Tao Shen et al.

Summary: The study revealed that MAPK4 promotes prostate cancer growth and castration resistance by activating GATA2/AR and AKT pathways. Activation of both GATA2/AR and AKT is necessary for MAPK4 tumor-promoting activity.

JOURNAL OF CLINICAL INVESTIGATION (2021)

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Article Multidisciplinary Sciences

MAPK6-AKT signaling promotes tumor growth and resistance to mTOR kinase blockade

Qinbo Cai et al.

Summary: The study revealed that MAPK6 activates AKT independently of mTORC2, potentially providing a major resistance pathway in cancer. Inhibiting MAPK6 sensitized cancer cells to mTOR kinase inhibitors. Overexpression of MAPK6 is associated with decreased overall survival in various cancer patients.

SCIENCE ADVANCES (2021)

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Article Biochemistry & Molecular Biology

SPOP-mediated ubiquitination and degradation of PDK1 suppresses AKT kinase activity and oncogenic functions

Qiwei Jiang et al.

Summary: The study reveals that E3 ligase SPOP mediates the ubiquitination and degradation of PDK1, and mutations in SPOP impair this process, leading to activation of the AKT kinase in prostate cancer. This highlights the oncogenic roles of SPOP loss-of-function mutations and PDK1 gain-of-function mutations in tumorigenesis through AKT activation.

MOLECULAR CANCER (2021)

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Article Medicine, Research & Experimental