Role of formins in tumor progression and metastasis in vivo

RhoA或RhoC等特异性Rho-GTP酶在侵袭性乳腺癌或黑色素瘤等多种肿瘤的侵袭和转移中起重要作用。然而，潜在的机制还没有被很好地理解。目前为止最大的一组Rho-GTP酶效应蛋白是由福尔马林代表的。Formins促进肌动蛋白细丝的从头形成，但也调节微管功能。肌动蛋白和微管动力学对细胞的运动和可塑性是绝对必要的。福尔马林在体内癌症进展和转移中的系统分析还没有进行过。在这个项目中，将对黑色素瘤细胞中的所有15种人类福尔马林进行RNA干扰(RNAi)，以确定哪些福尔马林在肿瘤转移和进展中具有特定功能。为此，将采用不同的小鼠转移模型和体外和体内的福尔明基因敲除策略来阐明特定的福尔马林是否以及如何主要参与转移疾病。这些研究将有助于确定哪些福尔马林在癌症扩散中发挥作用，从而可能代表有趣的治疗靶点。

Specific Rho-GTPases such as RhoA or RhoC play privotal roles for the invasion and metastasis of various tumours including aggressive breast carcinomas or melanomas. However, the underlying mechanisms are not well understood. The by far largest group of Rho-GTPase effector proteins is represented by the formins. Formins promote the de novo formation of actin filaments but also regulate microtubule function. Actin as well as microtubule dynamics are absolutely essential for cell motility and plasticity. A systematic analysis of formins in cancer progression and metastasis in vivo has not yet been performed. In this project, RNA interference (RNAi) against all 15 human formins in melanoma cells will be performed to identify which formins have a specific function in tumour metastasis and progression. To this end, different mouse metastasis models and strategies for formin knockdown ex vivo and in vivo will be employed to elucidate whether and how specific formins are principally involved in metastatic disease. These studies shall help to identify which formins play a role in the spread of cancer and thus may represent interesting therapeutic targets.