Drexel University College of Medicine, 245 N 15th Street, Philadelphia, PA 19102, USA.
Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Trends Cancer. 2020 Jun;6(6):478-488. doi: 10.1016/j.trecan.2020.02.021. Epub 2020 Mar 18.
Small GTPases of the RAS and RHO families are related signaling proteins that, when activated by growth factors or by mutation, drive oncogenic processes. While activating mutations in KRAS, NRAS, and HRAS genes have long been recognized and occur in many types of cancer, similar mutations in RHO family genes, such as RAC1 and RHOA, have only recently been detected as the result of extensive cancer genome-sequencing efforts and are linked to a restricted set of malignancies. In this review, we focus on the role of RAC1 signaling in malignant melanoma, emphasizing recent advances that describe how this oncoprotein alters melanocyte proliferation and motility and how these findings might lead to new therapeutics in RAC1-mutant tumors.
小 GTPases 的 RAS 和 RHO 家族相关的信号蛋白,当被生长因子或突变激活时,会驱动致癌过程。虽然 KRAS、NRAS 和 HRAS 基因的激活突变早已被认识到,并发生在许多类型的癌症中,但 RHO 家族基因,如 RAC1 和 RHOA 的类似突变,只是最近才在广泛的癌症基因组测序工作中被检测到,并与一系列有限的恶性肿瘤有关。在这篇综述中,我们专注于 RAC1 信号在恶性黑色素瘤中的作用,强调最近的进展,描述这种癌蛋白如何改变黑素细胞的增殖和迁移,以及这些发现如何导致 RAC1 突变肿瘤的新疗法。