SEMAPHORINSANDCANCER · The role of semaphorins and plexins in cancer progression and angiogenesis

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Project objective

Members of the scatter factor receptor family (Met and Ron) are key regulators in tumour invasion and metastasis. It has been shown that receptor over-expression, as well as specific mutations can lead to the constitutive activation of these oncogenes, which correlates with cancer progression. Two novel protein families phylo-genetically related to scatter factor receptors have been identified, plexins and semaphorin. Semaphorins control cell migration by binding to plexins, which compose one group of semaphor in receptors and are implicated in the regulation of cancer progression. Semaphorins can also bind to the tyrosine kinase receptor Met and neuropilin.Intriguingly, neuropilins also function as co-receptors for Vascular Endothelial Growth Factors (VEGFs), which are important regulators of angiogenesis. This project is aimed to understand the functional role and mechanisms whereby semaphorin signalling can regulate cancer progression. The function of several semaphorins and semaphorin receptors will be investigated in vivo, by means of lentiviral-mediated gene transfer, in a model of cancer progression from local invasiveness to metastasis. We will screen a number of semaphorins, plexins and neuropilins expressed in various cancers that are either metastatic to the lungs, or have no tendency to metastasise.The transfected cell lines will be used to establish tumour xenografts.). Further mechanistic control of specific semaphorins/plexins will be studied by testing the tumourigenic and metastatic potential of cancer cell lines engineered for their regulated expression, or translational knock-down (RNAi), or by expressing their wildtype and mutated receptors. We expect that this functional screening will provide a broad view of the oncogenic or onco-suppressor potential of different semaphorin genes, and will establish a proof of concept for studying further the encoded molecules as markers of tumour progression or potential cancer inhibitors.

Original text from CORDIS.

Participants

• INSTITUTE FOR CANCER RESEARCH AND TREATMENT - FONDAZIONE PIEMONTESE PER LA RICERCA SUL CANCRO · CANDIOLO (TORINO),CoordinatorCountry levelItaly

Links

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