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人类癌症中的SGK1:新出现的作用和机制

SGK1 in Human Cancer: Emerging Roles and Mechanisms.

作者信息

Sang Yiwen, Kong Piaoping, Zhang Shizhen, Zhang Lingyu, Cao Ying, Duan Xiuzhi, Sun Tao, Tao Zhihua, Liu Weiwei

机构信息

Department of Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

The Cancer Institute of the Second Affiliated Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Front Oncol. 2021 Jan 19;10:608722. doi: 10.3389/fonc.2020.608722. eCollection 2020.

Abstract

Serum and glucocorticoid-induced protein kinase 1 (SGK1) is a member of the "AGC" subfamily of protein kinases, which shares structural and functional similarities with the AKT family of kinases and displays serine/threonine kinase activity. Aberrant expression of SGK1 has profound cellular consequences and is closely correlated with human cancer. SGK1 is considered a canonical factor affecting the expression and signal transduction of multiple genes involved in the genesis and development of many human cancers. Abnormal expression of SGK1 has been found in tissue and may hopefully become a useful indicator of cancer progression. In addition, SGK1 acts as a prognostic factor for cancer patient survival. This review systematically summarizes and discusses the role of SGK1 as a diagnostic and prognostic biomarker of diverse cancer types; focuses on its essential roles and functions in tumorigenesis, cancer cell proliferation, apoptosis, invasion, metastasis, autophagy, metabolism, and therapy resistance and in the tumor microenvironment; and finally summarizes the current understanding of the regulatory mechanisms of SGK1 at the molecular level. Taken together, this evidence highlights the crucial role of SGK1 in tumorigenesis and cancer progression, revealing why it has emerged as a potential target for cancer therapy.

摘要

血清和糖皮质激素诱导蛋白激酶1(SGK1)是蛋白激酶“AGC”亚家族的成员,它与AKT激酶家族在结构和功能上具有相似性,并表现出丝氨酸/苏氨酸激酶活性。SGK1的异常表达具有深远的细胞影响,且与人类癌症密切相关。SGK1被认为是影响许多人类癌症发生和发展过程中多个基因表达和信号转导的一个典型因子。在组织中已发现SGK1的异常表达,有望成为癌症进展的有用指标。此外,SGK1可作为癌症患者生存的一个预后因素。本综述系统地总结并讨论了SGK1作为多种癌症类型的诊断和预后生物标志物的作用;重点阐述了其在肿瘤发生、癌细胞增殖、凋亡、侵袭、转移、自噬、代谢和治疗耐药性以及肿瘤微环境中的重要作用和功能;最后总结了目前在分子水平上对SGK1调控机制的认识。综上所述,这些证据突出了SGK1在肿瘤发生和癌症进展中的关键作用,揭示了它为何已成为癌症治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7297/7851074/30b5a2f1ca64/fonc-10-608722-g001.jpg

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