Hakem Anne, Sanchez-Sweatman Otto, You-Ten Annick, Duncan Gordon, Wakeham Andrew, Khokha Rama, Mak Tak W
Campbell Family Institute for Breast Cancer Research, Toronto, Ontario, M5G 2C1, Canada.
Genes Dev. 2005 Sep 1;19(17):1974-9. doi: 10.1101/gad.1310805. Epub 2005 Aug 17.
The Rho proteins are Ras-related guanosine triphosphatases (GTPases) that function in cytoskeletal reorganization, cell migration, and stress fiber and focal adhesion formation. Overexpression of RhoC enhances the ability of melanoma cells to exit the blood and colonize the lungs. However, in vivo confirmation of RhoC's role in metastasis has awaited a RhoC-deficient mouse model. Here we report the generation of RhoC-deficient mice and show that RhoC is dispensable for embryonic and post-natal development. We demonstrate that loss of RhoC does not affect tumor development but decreases tumor cell motility and metastatic cell survival leading to a drastic inhibition of metastasis.
Rho蛋白是与Ras相关的鸟苷三磷酸酶(GTP酶),在细胞骨架重组、细胞迁移以及应力纤维和粘着斑形成中发挥作用。RhoC的过表达增强了黑色素瘤细胞离开血液并在肺部定植的能力。然而,RhoC在转移中作用的体内证实一直等待着RhoC缺陷小鼠模型的出现。在此我们报告了RhoC缺陷小鼠的产生,并表明RhoC对于胚胎和出生后的发育并非必需。我们证明RhoC的缺失不影响肿瘤发展,但会降低肿瘤细胞的运动性和转移细胞的存活率,从而导致转移受到显著抑制。