PAX and MITF in signaling, Eye Development and Melanoma

Simon Saule
Scientific keywords: cell invasion, cell migration, metastasis, Mitf, uveal melanoma
Technics Used in the Lab: in vivo invasion, time-lapse video microscopy

Uveal melanoma (UM) is a rare neoplasm arising from melanocytes of the choroid or the ciliary body. One of its major clinical features is its high propensity to metastasize despite successful treatment of the primary tumour. We recently performed high-resolution expression profiling of uveal melanoma primary tumours, to identify metastasis inducing genes and focussed our attention on the phosphatase PTP4A3. Down regulation of PTP4A3 reduced metastasis spreading, and we confirmed with a naturally immunodeficient host chick embryo model that, one week after inoculation of PTP4A3, overexpressing UM cell lines were able to migrate and invade the avian blood system. Thus, in addition to increasing cell migration, PTP4A3 may also be involved in the regulation of protease-encoding genes. The downstream targets of PTP4A3 are not yet well defined, and we are focussing on proteins involved in protease function and cytosqueleton plasticity.