Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
School of Biological Engineering, Tianjin University of Science&Technology, Tianjin 301617, China.
Biochem Pharmacol. 2024 May;223:116141. doi: 10.1016/j.bcp.2024.116141. Epub 2024 Mar 16.
Small Ras homologous guanosine triphosphatase (Rho GTPase) family proteins are highly associated with tumorigenesis and development. As intrinsic exchange activity regulators of Rho GTPases, Rho guanine nucleotide exchange factors (RhoGEFs) have been demonstrated to be closely involved in tumor development and received increasing attention. They mainly contain two families: the diffuse B-cell lymphoma (Dbl) family and the dedicator of cytokinesis (Dock) family. More and more emphasis has been paid to the Dbl family members for their abnormally high expression in various cancers and their correlation to poor prognosis. In this review, the common and distinctive structures of Dbl family members are discussed, and their roles in cancer are summarized with a focus on Ect2, Tiam1/2, P-Rex1/2, Vav1/2/3, Trio, KALRN, and LARG. Significantly, the strategies targeting Dbl family RhoGEFs are highlighted as novel therapeutic opportunities for cancer.
小分子 Ras 同源鸟苷三磷酸酶（Rho GTPase）家族蛋白与肿瘤的发生和发展高度相关。Rho GTPase 的内在交换活性调节剂 Rho 鸟苷酸交换因子（RhoGEFs）已被证明与肿瘤的发展密切相关，并受到越来越多的关注。它们主要包含两个家族：弥漫性 B 细胞淋巴瘤（Dbl）家族和胞质分裂（Dock）家族。越来越多的人关注 Dbl 家族成员，因为它们在各种癌症中的异常高表达及其与预后不良的相关性。在这篇综述中，讨论了 Dbl 家族成员的常见和独特结构，并总结了它们在癌症中的作用，重点介绍了 Ect2、Tiam1/2、P-Rex1/2、Vav1/2/3、Trio、KALRN 和 LARG。值得注意的是，针对 Dbl 家族 RhoGEFs 的策略被强调为癌症的新治疗机会。
