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Rho GTPases 在干细胞调控中的作用。

Role of Rho GTPases in stem cell regulation.

机构信息

Division of Experimental Hematology and Cancer Biology, Children's Hospital Medical Center, University of Cincinnati, 3333 Burnet Avenue, Cincinnati, OH 45229, U.S.A.

Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Biochem Soc Trans. 2021 Dec 17;49(6):2941-2955. doi: 10.1042/BST20211071.

Abstract

The future of regenerative medicine relies on our understanding of stem cells which are essential for tissue/organ generation and regeneration to maintain and/or restore tissue homeostasis. Rho family GTPases are known regulators of a wide variety of cellular processes related to cytoskeletal dynamics, polarity and gene transcription. In the last decade, major new advances have been made in understanding the regulatory role and mechanism of Rho GTPases in self-renewal, differentiation, migration, and lineage specification in tissue-specific signaling mechanisms in various stem cell types to regulate embryonic development, adult tissue homeostasis, and tissue regeneration upon stress or damage. Importantly, implication of Rho GTPases and their upstream regulators or downstream effectors in the transformation, migration, invasion and tumorigenesis of diverse cancer stem cells highlights the potential of Rho GTPase targeting in cancer therapy. In this review, we discuss recent evidence of Rho GTPase signaling in the regulation of embryonic stem cells, multiple somatic stem cells, and cancer stem cells. We propose promising areas where Rho GTPase pathways may serve as useful targets for stem cell manipulation and related future therapies.

摘要

再生医学的未来依赖于我们对干细胞的理解,干细胞对于组织/器官的生成和再生以维持和/或恢复组织内稳态至关重要。Rho 家族 GTP 酶是与细胞骨架动力学、极性和基因转录相关的各种细胞过程的重要调节剂。在过去的十年中,人们在理解 Rho GTP 酶在各种干细胞类型中的自我更新、分化、迁移和谱系特化中的调控作用和机制方面取得了重大新进展,以调节胚胎发育、成人组织内稳态以及应激或损伤后的组织再生。重要的是,Rho GTP 酶及其上游调节剂或下游效应物在多种癌症干细胞的转化、迁移、侵袭和致瘤性中的作用,突出了 Rho GTP 酶靶向在癌症治疗中的潜力。在这篇综述中,我们讨论了 Rho GTP 酶信号在胚胎干细胞、多种体干细胞和癌症干细胞调控中的最新证据。我们提出了 Rho GTP 酶途径可能作为干细胞操作和相关未来治疗的有用靶点的有前景的领域。

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