The work of our team concern messengers of receptors involved in tumor progression: growth factors of the family of EGF and neuropeptide VIP family. The four receptor tyrosine kinase family EGFR / ErbB activated in response to extracellular signals, cytoplasmic signaling pathways (MAPK, PI3K) regulating gene expression involved in the development, proliferation and cell differentiation. Overexpression of these receptors or their ligands, or the appearance of mutations in the kinase domain are involved in the development and progression of many types of human cancers (breast, colon, prostate ..).
Neuropeptides are molecules usually released by neurons of the central and peripheral nervous systems and act as hormones, growth factors, neurotransmitters or neuromodulators. They bind to 3 membrane receptors of the family of receptors coupled to G proteins, called VPAC1, VPAC2 and PAC1. These receptors and / or their ligands (VIP / PACAP) are expressed in many types of cancer (lung, prostate, colon, astrocytoma, glioblastoma) where they participate in tumor progression. Receptors for VIP and those of the ErbB family, are known to be localized to the plasma membrane. Thus they constitute preferred therapeutic targets, and numerous anticancer strategies aimed at inactivating these receptors by blocking activation by ligand in the extracellular domains and / or inhibiting the associated signaling pathways. However, resistance mechanisms have been identified and could involve nuclear forms of these receptors. The four ErbB receptors have been observed at the nuclear level, either in whole form or in a truncated form, and this in many tumor models (colon, prostate). In the case of VIP receptors, some studies have shown the presence in their nuclei or nuclear membrane in lymphocytes but also in breast cancer and adenocarcinomas of the colon.
Our research team works on :
1) Gliomas, ErbB family receptor and VIP-receptor system: The EGF receptor (EGFR) is mutated or overexpressed in 20 to 50% of glioblastoma (GBM). The VIP-receptor system regulates the expression and EGFR transactivation different in cancers of the prostate, breast and lung. We study this regulation in GBM, and we focus more specifically on nuclear forms of the ErbB3 receptor and VIP receptors.
2) Prostate cancer, ErbB3, VIP receptor system and tumor progression: Nuclear ErB3 expression is associated with the progression of prostate cancer (CaP) but the mechanisms underlying this process are not known. Similarly, the VIP-receptor system has an oncogenic role found in cancers of the prostate in which it takes part in the invasion. We analyze the transactivation of ErbB3 ways by the VIP-receptor system and its relationship with tumor progression.
3) Comparative analysis of regulation by the VIP-receptor system of cell migration in PCa and GBM. In CaP, VIP-receptors induces migration system while it inhibits in cells of GBM. By transcriptome analysis we are looking for the expression of genes involved in these opposing responses.
4) Prodrugs targeting and isolation of new molecules with anti-cancer potential from natural products