J. Guillermet-Guibert

Cancer cells communicate in the organ where they develop: this communication aim to prevent the host to kill them, but cancer cells also use these signals at their advantage to create a favorable environment towards their development. This communication “network” in a tumour called signal network is thus the result of their interaction but also an Achille’s heel that could be annihilated by targeted therapies.

We accumulated data demonstrating that primary tumour development and its development at distance (metastase) are directed by a family of molecules at the cross bridge of signaling networks, PI3Ks.

They are present in 8 forms, so called “isoforms”, both in cancer cells and in surrounding cells. We demonstrated that each of them have different actions.

Class I phosphoinositide-3-kinases (PI3Ks) (PI3Kα, β, γ, δ) are a central node of cell signalling and act as an integrator of multiple signals including oncogenes. The downstream PI3K/Akt/mTOR signalling pathway has a diverse array of functions, including the regulation of cellular survival, differentiation and stem cell-like properties, growth, proliferation, metabolism, migration and angiogenesis. It is one of the most frequently activated pathogenic signalling routes in Human cancers making it an important target for innovative anticancer drug development. Class II and III PI3K enzymes are critical regulators of intracellular vesicular trafficking and as such they display critical role in the regulation of endocytosis, exocytosis and autophagy. Their function in pancreatic physiopathology is unknown.

Our programs & team at a glance

Phd program – PI3K in health and disease – Arc project

Our laboratory belong to an European consortium dedicated to the study of PI3K signaling in health and disease. Our two PhD early stage researchers, Silvia Arcucci and Fernanda Ramos-Delgado, dissect the role of class I PI3Kβ and class II and III PI3K in pancreas physiology and disease. Please watch the video of presentation of the program here.

Labex TOUCAN – Studying resistance to signal-targeted therapies

Our laboratory is part of the Labex program, whereby we investigate through quantitative phosphoproteomics approaches the redundancy of signal networks controlled by each class I PI3K in a cancer setting.

RADIANCE program

In 1974, George Emile Palade’s research achievements on pancreatic acinar cell ultrastructure were recognized by a Nobel Prize: exocrine acinar cells are highly differentiated cells towards the production and the timely secretion of digestive enzymes. They represent a paradigm physiological cell model to study intracellular vesicular trafficking and protein secretion. It is starting to be accepted that autophagy, the intracellular degradation system, plays a key role in the physiopathology of chronic pancreatitis. Using innovative mouse models and single-cell approaches, RADIANCE will aim to demonstrate that the class III PI3K Vps34-regulated autophagic flux allows the regeneration of differentiated pancreatic exocrine cells, knowledge relevant for the curative treatment of chronic pancreatitis patients.

Last update december 2019