Barras David, Widmann Christian
Department of Physiology, University of Lausanne, Bugnon 7, 1005, Lausanne, Switzerland.
Cancer Metastasis Rev. 2014 Mar;33(1):87-100. doi: 10.1007/s10555-013-9458-0.
Metastases are responsible for most cancer-related deaths. One of the hallmarks of metastatic cells is increased motility and migration through extracellular matrixes. These processes rely on specific small GTPases, in particular those of the Rho family. Deleted in liver cancer-1 (DLC1) is a tumor suppressor that bears a RhoGAP activity. This protein is lost in most cancers, allowing malignant cells to proliferate and disseminate in a Rho-dependent manner. However, DLC1 is also a scaffold protein involved in alternative pathways leading to tumor and metastasis suppressor activities. Recently, substantial information has been gathered on these mechanisms and this review is aiming at describing the potential and known alternative GAP-independent mechanisms allowing DLC1 to impair migration, invasion, and metastasis formation.
转移是大多数癌症相关死亡的原因。转移细胞的一个标志是通过细胞外基质增加运动性和迁移能力。这些过程依赖于特定的小GTP酶,尤其是Rho家族的那些酶。肝癌缺失-1(DLC1)是一种具有RhoGAP活性的肿瘤抑制因子。这种蛋白质在大多数癌症中缺失,使恶性细胞能够以Rho依赖的方式增殖和扩散。然而,DLC1也是一种支架蛋白,参与导致肿瘤和转移抑制活性的替代途径。最近,已经收集了大量关于这些机制的信息,本综述旨在描述允许DLC1损害迁移、侵袭和转移形成的潜在和已知的独立于GAP的替代机制。