Débute à 

Salle M-415
2900, boul. Édouard-Montpetit, Montréal
Montréal (Québec) Canada  H3T 1J4

Conférence de chimie avec le professeur Jeffrey Keillor de l'Université d'Ottawa.

Hôte : Joelle Pelletier

Résumé
Recent evidence has shown that tissue transglutaminase (TG2) is a key player in the metastatic progression of cancer. TG2 is an enzyme that was first identified for its ability to mediate the extracellular cross-linking of proteins through the formation of isopeptide bonds; this transamidation reaction is catalysed by the enzyme when it adopts an extended conformation. However, TG2 is also known to play a role as a GTP binding protein in intracellular G protein signalling, for which it adopts a dramatically more compact conformation. Most recently, TG2 expression has been implicated in inducing the epithelial-mesenchymal transition (EMT) in ovarian, breast and epidermal cancer stem cells, contributing to their development of drug resistance and metastatic competence.

Over the past ~20 years of research into TG2 mechanism and inhibition, we have developed many reversible and irreversible inhibitors. Recent results will be presented, where we have demonstrated that our targeted covalent inhibitors are able to modulate the conformation of TG2 and abolish both its transamidation and GTP-binding activities, in vitro and in living human cells. Furthermore, collaborative efforts have shown that several of our inhibitors are able to halt the EMT of epidermal cancer stem cells (CSCs), through a mechanism of action that involves perturbation of a specific signalling pathway critical to CSC survival.

Website:  Keillor-research-group.com 

Twitter account @theKeillors

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