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TRPM7离子通道:在乳腺癌中的致癌作用及治疗潜力

TRPM7 Ion Channel: Oncogenic Roles and Therapeutic Potential in Breast Cancer.

作者信息

Cordier Clément, Prevarskaya Natalia, Lehen'kyi V'yacheslav

机构信息

Laboratory of Cell Physiology, INSERM U1003, Laboratory of Excellence Ion Channels Science and Therapeutics, Department of Biology, Faculty of Science and Technologies, University of Lille, 59650 Villeneuve d'Ascq, France.

University Lille, Inserm, U1003-PHYCEL-Physiologie Cellulaire, F-59000 Lille, France.

出版信息

Cancers (Basel). 2021 Dec 16;13(24):6322. doi: 10.3390/cancers13246322.

Abstract

The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a divalent cations permeant channel but also has intrinsic serine/threonine kinase activity. It is ubiquitously expressed in normal tissues and studies have indicated that it participates in important physiological and pharmacological processes through its channel-kinase activity, such as calcium/magnesium homeostasis, phosphorylation of proteins involved in embryogenesis or the cellular process. Accumulating evidence has shown that TRPM7 is overexpressed in human pathologies including breast cancer. Breast cancer is the second leading cause of cancer death in women with an incidence rate increase of around 0.5% per year since 2004. The overexpression of TRPM7 may be associated with a poor prognosis in breast cancer patients, so more efforts are needed to research a new therapeutic target. TRPM7 regulates the levels of Ca, which can alter the signaling pathways involved in survival, cell cycle progression, proliferation, growth, migration, invasion, epithelial-mesenchymal transition and thus determines cell behavior, promoting tumor development. This work provides a complete overview of the TRPM7 ion channel and its main involvements in breast cancer. Special consideration is given to the modulation of the channel as a potential target in breast cancer treatment by inhibition of proliferation, migration and invasion. Taken together, these data suggest the potential exploitation of TRPM7 channel-kinase as a therapeutic target and a diagnostic biomarker.

摘要

瞬时受体电位褪黑素亚家族成员7(TRPM7)是一种二价阳离子通透通道,但也具有内在的丝氨酸/苏氨酸激酶活性。它在正常组织中广泛表达,研究表明它通过其通道激酶活性参与重要的生理和药理过程,如钙/镁稳态、胚胎发育或细胞过程中相关蛋白质的磷酸化。越来越多的证据表明,TRPM7在包括乳腺癌在内的人类疾病中过度表达。乳腺癌是女性癌症死亡的第二大主要原因,自2004年以来发病率每年约上升0.5%。TRPM7的过度表达可能与乳腺癌患者的不良预后有关,因此需要更多努力来研究新的治疗靶点。TRPM7调节钙水平,这可以改变参与生存、细胞周期进程、增殖、生长、迁移、侵袭、上皮-间质转化的信号通路,从而决定细胞行为,促进肿瘤发展。这项工作全面概述了TRPM7离子通道及其在乳腺癌中的主要作用。特别关注通过抑制增殖、迁移和侵袭来调节该通道作为乳腺癌治疗潜在靶点的情况。综上所述,这些数据表明TRPM7通道激酶有作为治疗靶点和诊断生物标志物的潜在开发价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d13/8699295/dd655bb5b93d/cancers-13-06322-g001.jpg

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