Developmental Biology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Cell Signal. 2011 Jun;23(6):969-79. doi: 10.1016/j.cellsig.2010.10.022. Epub 2010 Oct 30.
Rho guanosine triphosphatases (GTPases) are a family of small proteins which function as molecular switches in a variety of signaling pathways following stimulation of cell surface receptors. RhoGTPases regulate numerous cellular processes including cytoskeleton organization, gene transcription, cell proliferation, migration, growth and cell survival. Because of their central role in regulating processes that are dysregulated in cancer, it seems reasonable that defects in the RhoGTPase pathway may be involved in the development of cancer. RhoGTPase activity is regulated by a number of protein families: guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs) and guanine nucleotide-dissociation inhibitors (GDIs). This review discusses the participation of RhoGTPases and their regulators, especially GEFs in human cancers. In particular, we focus on the involvement of the RhoGTPase GEF, Vav1, a hematopoietic specific signal transducer which is involved in human neuroblastoma, pancreatic ductal carcinoma and lung cancer. Finally, we summarize recent advances in the design and application of a number of molecules that specifically target individual RhoGTPases or their regulators or effectors, and discuss their potential for cancer therapy.
Rho 鸟苷三磷酸酶（GTPases）是一个小蛋白家族，在细胞表面受体受到刺激后，作为多种信号通路中的分子开关发挥作用。RhoGTPases 调节许多细胞过程，包括细胞骨架组织、基因转录、细胞增殖、迁移、生长和细胞存活。由于它们在调节癌症中失调的过程中起着核心作用，因此 RhoGTPase 途径的缺陷可能参与癌症的发展似乎是合理的。RhoGTPase 活性受许多蛋白质家族的调节：鸟苷核苷酸交换因子（GEFs）、GTPase 激活蛋白（GAPs）和鸟苷核苷酸解离抑制剂（GDIs）。这篇综述讨论了 RhoGTPases 及其调节剂，特别是 GEFs 在人类癌症中的参与。特别是，我们专注于 RhoGTPase GEF，Vav1 的参与，Vav1 是一种造血特异性信号转导物，参与人类神经母细胞瘤、胰腺导管腺癌和肺癌。最后，我们总结了一些专门针对单个 RhoGTPases 或其调节剂或效应物的分子的设计和应用的最新进展，并讨论了它们在癌症治疗中的潜力。
