RHO GTPases are key regulators of the cytoskeletal architecture, which impacts on a broad range of biological processes in malignant cells including motility, invasion and metastasis, thereby affecting tumor progression. One of the constrains during cell migration, is the diameter of the pores through which cells pass. In this respect, the size and shape of the nucleus poses a major limitation. Therefore, enhanced nuclear plasticity can promote cell migration. Nuclear morphology is determined in part through the cytoskeleton, which connects to the nucleoskeleton through the LINC complex. Here, we unravel the role of RAC1 as an orchestrator of nuclear morphology in melanoma cells. We demonstrate that activated RAC1 promotes nuclear alterations through its effector PAK1 and the tubulin cytoskeleton, thereby enhancing migration and intravasation of melanoma cells. Disruption of the LINC complex prevented RAC1-induced nuclear alterations and the invasive properties of melanoma cells. Thus, RAC1 induces nuclear morphology alterations through microtubules and the LINC complex to promote an invasive phenotype in melanoma cells.

RHO GTPases是细胞骨架结构的关键调节因子，它影响恶性细胞的广泛生物学过程，包括运动性，侵袭和转移，从而影响肿瘤的进展。细胞迁移期间的限制之一是细胞通过的孔的直径。在这方面，核的大小和形状构成主要限制。因此，增强核可塑性可以促进细胞迁移。核形态部分地通过细胞骨架来确定，该细胞骨架通过LINC复合物连接到核骨架。在这里，我们揭示了RAC1作为黑色素瘤细胞核形态协调器的作用。我们证明，激活的RAC1通过其效应物PAK1和微管蛋白细胞骨架促进核改变，从而增强黑色素瘤细胞的迁移和侵袭。LINC复合物的破坏阻止了RAC1诱导的核改变和黑素瘤细胞的侵袭特性。因此，RAC1通过微管和LINC复合物诱导核形态改变，从而促进黑色素瘤细胞的侵袭性表型。