Crosas-Molist Eva, Samain Remi, Kohlhammer Leonie, Orgaz Jose L, George Samantha L, Maiques Oscar, Barcelo Jaume, Sanz-Moreno Victoria
Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
Instituto de Investigaciones Biomédicas "Alberto Sols," Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
Physiol Rev. 2022 Jan 1;102(1):455-510. doi: 10.1152/physrev.00045.2020. Epub 2021 Sep 20.
Rho GTPases are a family of small G proteins that regulate a wide array of cellular processes related to their key roles controlling the cytoskeleton. Cancer is a multistep disease caused by the accumulation of genetic mutations and epigenetic alterations, from the initial stages of cancer development when cells in normal tissues undergo transformation, to the acquisition of invasive and metastatic traits, responsible for a large number of cancer related deaths. In this review, we discuss the role of Rho GTPase signaling in cancer in every step of disease progression. Rho GTPases contribute to tumor initiation and progression, by regulating proliferation and apoptosis, but also metabolism, senescence, and cancer cell stemness. Rho GTPases play a major role in cell migration and in the metastatic process. They are also involved in interactions with the tumor microenvironment and regulate inflammation, contributing to cancer progression. After years of intensive research, we highlight the importance of relevant models in the Rho GTPase field, and we reflect on the therapeutic opportunities arising for cancer patients.
Rho GTP酶是一类小G蛋白家族，它们调节与控制细胞骨架的关键作用相关的广泛细胞过程。癌症是一种多步骤疾病，由基因突变和表观遗传改变的积累引起，从正常组织中的细胞发生转化的癌症发展初始阶段，到获得侵袭性和转移性特征，这些特征导致大量与癌症相关的死亡。在本综述中，我们讨论了Rho GTP酶信号在疾病进展的每个步骤中在癌症中的作用。Rho GTP酶通过调节增殖和凋亡，还通过调节代谢、衰老和癌细胞干性，促进肿瘤的起始和进展。Rho GTP酶在细胞迁移和转移过程中起主要作用。它们还参与与肿瘤微环境的相互作用并调节炎症，促进癌症进展。经过多年的深入研究，我们强调了Rho GTP酶领域相关模型的重要性，并思考了为癌症患者带来的治疗机会。
