The work of our team concern messengers of receptors involved in tumor progression: growth factors of the EGF family and the family of neuropeptides VIP.
The four receptors with tyrosine kinase activity of the EGFR family/ErbB activate cell proliferation and differentiation, in response to extracellular signals or cytoplasmic signaling pathways (MAPK, PI3K). Overexpression of these receptors or their ligands, or mutations in the kinase domain are involved in the development and progression of many types of human cancers (breast, colon, prostate ..).
Neuropeptides are molecules normally 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 G protein-coupled receptor, known as VPAC1, VPAC2 and PAC1. These receptors and / or their ligands (VIP / PACAP) are expressed in many types of cancer (lung, prostate, colon, astrocytomas, glioblastomas), where they are involved in tumor progression.
Receptors for VIP and those of the ErbB family, are known to be localized at the plasma membrane. Thus they constitute preferred therapeutic targets and many anti-cancer strategies aimed at inactivating these receptors by blocking activation by ligand in the extracellular domains and/or by inhibiting the associated signaling pathways.
However, resistance mechanisms have been identified and could involve nuclear forms of these receptors. Four ErbB receptors have been observed in the nucleus or 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 their presence in the nuclei or nuclear membrane in lymphocytes but also in breast cancer and adenocarcinoma of the colon.
Our team research work focuses on four areas:
1) gliomas, receptors of the ErbB family and VIP-receptor system:
The EGF receptor (EGFR) is mutated or overexpressed in 20-50% 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 specifically nuclear forms of the ErbB3 receptor and VIP receptors.
2) Prostate cancer, ErbB3, VIP-receptor system and tumor progression:
Nuclear expression of ErB3 is associated with the progression of prostate cancer (PCa) but the mechanisms underlying this process are not known. Similarly, the VIP-receptor system has proven an oncogenic role in prostate cancer in which it participates in invasion. We analyze the transactivation of ErbB3 channels 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 Pca, the VIP-receptor system induces migration while inhibing it in GBM cells. By transcriptomic analysis we seek the expression of genes involved in these opposing responses.
4) Through collaborations, we develop prodrugs targeting signaling pathways of cancer and we isolate new molecules with anti-cancer potential from plant extracts (Congo, Morocco).