University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Department of Pharmacology, Chapel Hill, NC 27599, USA.
University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Department of Pharmacology, Chapel Hill, NC 27599, USA.
Trends Cancer. 2022 Aug;8(8):655-669. doi: 10.1016/j.trecan.2022.04.005. Epub 2022 May 12.
RAS and RHO GTPases function as signaling nodes that regulate diverse cellular processes. Whereas RAS mutations were identified in human cancers nearly four decades ago, only recently have mutations in two RHO GTPases, RAC1 and RHOA, been identified in cancer. RAS mutations are found in a diverse spectrum of human cancer types. By contrast, RAC1 and RHOA mutations are associated with distinct and restricted cancer types. Despite a conservation of RAS and RAC1 residues that comprise mutational hotspots, RHOA mutations comprise highly divergent hotspots. Whereas RAS and RAC1 act as oncogenes, RHOA may act as both an oncogene and a tumor suppressor. Thus, while RAS and RHO each take different mutational paths, they arrive at the same biological destination as cancer drivers.
RAS 和 RHO GTPases 作为信号节点，调节多种细胞过程。虽然 RAS 突变在近四十年前就已经在人类癌症中被发现，但直到最近才发现两种 RHO GTPases（RAC1 和 RHOA）在癌症中发生突变。RAS 突变存在于多种人类癌症类型中。相比之下，RAC1 和 RHOA 突变与特定且受限的癌症类型相关。尽管 RAS 和 RAC1 突变热点区域的残基具有保守性，但 RHOA 突变热点区域具有高度的差异性。虽然 RAS 和 RAC1 作为致癌基因发挥作用，但 RHOA 可能既是致癌基因又是肿瘤抑制基因。因此，尽管 RAS 和 RHO 各走不同的突变途径，但它们作为癌症驱动基因到达了相同的生物学终点。
