Role of formins in tumor progression and metastasis in vivo

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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.