CLIC1 调控胶质母细胞瘤中的癌症干细胞。

CLIC1 regulation of cancer stem cells in glioblastoma.

机构信息

Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada; Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada.

Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada; Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada; Regenerative Medicine Program and Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.

出版信息

Curr Top Membr. 2023;92:99-123. doi: 10.1016/bs.ctm.2023.09.004. Epub 2023 Sep 29.

DOI:10.1016/bs.ctm.2023.09.004

PMID:38007271

Abstract

Chloride intracellular channel 1 (CLIC1) has emerged as a therapeutic target in various cancers. CLIC1 promotes cell cycle progression and cancer stem cell (CSC) self-renewal. Furthermore, CLIC1 is shown to play diverse roles in proliferation, cell volume regulation, tumour invasion, migration, and angiogenesis. In glioblastoma (GB), CLIC1 facilitates the G1/S phase transition and tightly regulates glioma stem-like cells (GSCs), a rare population of self-renewing CSCs with central roles in tumour resistance to therapy and tumour recurrence. CLIC1 is found as either a monomeric soluble protein or as a non-covalent dimeric protein that can form an ion channel. The ratio of dimeric to monomeric protein is altered in GSCs and depends on the cell redox state. Elucidating the mechanisms underlying the alterations in CLIC1 expression and structural transitions will further our understanding of its role in GSC biology. This review will highlight the role of CLIC1 in GSCs and its significance in facilitating different hallmarks of cancer.

摘要

氯离子细胞内通道 1（CLIC1）已成为各种癌症的治疗靶点。CLIC1 促进细胞周期进程和癌症干细胞（CSC）自我更新。此外，CLIC1 被证明在增殖、细胞体积调节、肿瘤侵袭、迁移和血管生成中发挥多种作用。在胶质母细胞瘤（GB）中，CLIC1 促进 G1/S 期过渡，并严格调节神经胶质瘤干细胞（GSCs），GSCs 是一类具有自我更新能力的罕见 CSC 群体，在肿瘤对治疗的耐药性和肿瘤复发中起着核心作用。CLIC1 可以作为单体可溶性蛋白或非共价二聚体蛋白存在，形成离子通道。GSCs 中二聚体蛋白与单体蛋白的比例发生改变，并且依赖于细胞的氧化还原状态。阐明 CLIC1 表达和结构转变的改变背后的机制将进一步加深我们对其在 GSC 生物学中作用的理解。本文综述了 CLIC1 在 GSCs 中的作用及其在促进癌症不同特征中的意义。