Dbl family RhoGEFs in cancer: different roles and targeting strategies

[Display omitted] 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 invo...

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Published in:Biochemical pharmacology 2024-05, Vol.223, p.116141, Article 116141
Main Authors: Chen, Xin-Yi, Cheng, Ao-Yu, Wang, Zi-Ying, Jin, Jin-Mei, Lin, Jia-Yi, Wang, Bei, Guan, Ying-Yun, Zhang, Hao, Jiang, Yi-Xin, Luan, Xin, Zhang, Li-Jun
Format: Article
Language:English
Subjects:
Cancer
Dbl family
Rho guanine nucleotide exchange factors
Targeting strategy
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Summary:[Display omitted] 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.
ISSN:0006-2952
1873-2968
1873-2968
DOI:10.1016/j.bcp.2024.116141