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作者

Fei Meng Huiyan Li Yijie Wang Zhiming Zheng Yan Chen

作者单位

³Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China ²These authors contributed equally. ¹Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Center for Cell Structure and Function, Modem Industry Institute of Biomedicine, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China

刊名

Cell Investigation

年份

2025

卷号

Vol.1 No.4

页码

100046

ISSN

3050-5380

关键词

AKT PI3K PDK1 MTORC2 Post-translational modification Cancer

摘要

The serine/threonine kinase AKT is a central signaling node frequently dysregulated in cancer, integrating inputs from both canonical PI3K-dependent and alternative activation pathways to drive tumorigenesis. In this review, we systematically summarize the complex regulatory mechanisms governing AKT activation, with a focus on oncogenic alterations such as PIK3CA mutations and PTEN loss. Moreover, we discuss the distinct functional contributions of AKT isoforms in cancer progression and provide ...更多

The serine/threonine kinase AKT is a central signaling node frequently dysregulated in cancer, integrating inputs from both canonical PI3K-dependent and alternative activation pathways to drive tumorigenesis. In this review, we systematically summarize the complex regulatory mechanisms governing AKT activation, with a focus on oncogenic alterations such as PIK3CA mutations and PTEN loss. Moreover, we discuss the distinct functional contributions of AKT isoforms in cancer progression and provide a comprehensive review of how diverse post-translational modifications, including ubiquitination, methylation, SUMOylation, palmitoylation, and O-GlcNAcylation, fine-tune AKT activity, localization, and stability. Recent structural and mechanistic insights into membrane recruitment, conformational changes, and compensatory reactivation under therapeutic pressure are discussed. The review synthesizes the current challenges in targeting the AKT pathway, emphasizing the necessity for innovative strategies that address its complexity, adaptive resistance, and the potential of isoform-specific and combination therapies.收起

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