Malignant carcinomas are often characterized by metastasis, the movement of carcinoma cells from a primary site to colonize distant organs. For metastasis to occur, carcinoma cells first must adopt a pro-migratory phenotype and move through the surrounding stroma towards a blood or lymphatic vessel. Currently, there are very limited possibilities to target these processes therapeutically.

The family of Rho GTPases is an ubiquitously expressed division of GTP-binding proteins involved in the regulation of cytoskeletal dynamics and intracellular signaling. The best characterized members of the Rho family GTPases are RhoA, Rac1 and Cdc42. Abnormalities in Rho GTPase function have major consequences for cancer progression. Rho GTPase activation is driven by cell surface receptors that activate GTP exchange factors (GEFs) and GTPase-activating proteins (GAPs). In this review, we summarize our current knowledge on Rho GTPase function in the regulation of metastasis. We will focus on key discoveries in the regulation of epithelial-mesenchymal-transition (EMT), cell-cell junctions, formation of membrane protrusions, plasticity of cell migration and adaptation to a hypoxic environment. In addition, we will emphasize on crosstalk between Rho GTPase family members and other important oncogenic pathways, such as cyclic AMP-mediated signaling, canonical Wnt/β-catenin, Yes-associated protein (YAP) and hypoxia inducible factor 1α (Hif1α) and provide an overview of the advancements and challenges in developing pharmacological tools to target Rho GTPase and the aforementioned crosstalk in the context of cancer therapeutics.

恶性癌通常以转移为特征，转移是癌细胞从原发部位向远处器官定植。为使转移发生，癌细胞首先必须采用促迁移表型，并通过周围的基质移向血液或淋巴管。当前，在治疗上靶向这些过程的可能性非常有限。

Rho GTPases家族是GTP结合蛋白普遍表达的分裂，参与调节细胞骨架动力学和细胞内信号传导。Rho系列GTPases最具特征的成员是RhoA，Rac1和Cdc42。Rho GTPase功能异常对癌症进展有重要影响。Rho GTPase激活由激活GTP交换因子（GEF）和GTPase激活蛋白（GAP）的细胞表面受体驱动。在这篇综述中，我们总结了我们目前对Rho GTPase在转移调节中的功能的了解。我们将重点关注上皮-间质转化（EMT），细胞-细胞连接，膜突起形成，细胞迁移的可塑性以及对低氧环境的适应性调节方面的关键发现。此外，