Rodenburg Wessel S, van Buul Jaap D
Molecular Cell Biology Lab at Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands.
Leeuwenhoek Centre for Advanced Microscopy, Section Molecular Cytology at Swammerdam Institute for Life Sciences at University of Amsterdam, Amsterdam, the Netherlands.
Vasc Biol. 2021 Sep 14;3(1):R77-R95. doi: 10.1530/VB-21-0008. eCollection 2021.
Rho GTPases are small signalling G-proteins that are central regulators of cytoskeleton dynamics, and thereby regulate many cellular processes, including the shape, adhesion and migration of cells. As such, Rho GTPases are also essential for the invasive behaviour of cancer cells, and thus involved in several steps of the metastatic cascade, including the extravasation of cancer cells. Extravasation, the process by which cancer cells leave the circulation by transmigrating through the endothelium that lines capillary walls, is an essential step for metastasis towards distant organs. During extravasation, Rho GTPase signalling networks not only regulate the transmigration of cancer cells but also regulate the interactions between cancer and endothelial cells and are involved in the disruption of the endothelial barrier function, ultimately allowing cancer cells to extravasate into the underlying tissue and potentially form metastases. Thus, targeting Rho GTPase signalling networks in cancer may be an effective approach to inhibit extravasation and metastasis. In this review, the complex process of cancer cell extravasation will be discussed in detail. Additionally, the roles and regulation of Rho GTPase signalling networks during cancer cell extravasation will be discussed, both from a cancer cell and endothelial cell point of view.
Rho GTP酶是一类小型信号G蛋白，是细胞骨架动力学的核心调节因子，从而调控许多细胞过程，包括细胞的形状、黏附及迁移。因此，Rho GTP酶对于癌细胞的侵袭行为也至关重要，进而参与转移级联反应的多个步骤，包括癌细胞的外渗。外渗是指癌细胞通过穿过毛细血管壁内衬的内皮细胞而离开循环系统的过程，是向远处器官转移的关键步骤。在癌细胞外渗过程中，Rho GTP酶信号网络不仅调节癌细胞的迁移，还调节癌细胞与内皮细胞之间的相互作用，并参与内皮屏障功能的破坏，最终使癌细胞外渗至下层组织并可能形成转移灶。因此，靶向癌症中的Rho GTP酶信号网络可能是抑制外渗和转移的有效方法。在这篇综述中，将详细讨论癌细胞外渗的复杂过程。此外，还将从癌细胞和内皮细胞的角度讨论Rho GTP酶信号网络在癌细胞外渗过程中的作用和调控。
