Intestinal epithelial cell proliferation in physiology and cancer
Inserm U1016-CNRS UMR8104-Université Paris Descartes,
Département Développement, Reproduction et Cancer,
Equipe Oncogenèse des épithéliums digestifs,
24 rue du Faubourg Saint Jacques, 75014 Paris
Tel.33(0)1 44 41 25 69 – Fax 33(0)1 44 41 24 21
Presentation of the team
Béatrice Romagnolo, DR2 INSERM email@example.com
Team members 2015
Coralie Trentesaux, doctorante
Marie Fraudeau, AI
Julie Lemarchand, AI
Intestine, stem cells, cancer, autophagy, Wnt/β-catenin signaling, murine models
The aim of our group is to identify the molecular mechanisms involved in self-renewal and maintenance of intestinal stem cells (ISC) and to study the associated deregulated mechanisms involved in tumor development.
Historically, our research activity was centered on the study of the Wnt/β-catenin signaling. Our work has helped to demonstrate the fundamental role of this pathway in the proliferation of ISC and progenitors but also in the specification of the Paneth cell lineage which contributes to the ISC niche. Our projects pursue the understanding of the factors required for the functional integrity of ISC by analyzing conditional knockout mutant mice and organoids culture.
A second aim of our research is to study the consequences of deregulation of the Wnt/β-catenin signaling in the gut epithelium. Approximately 80% of sporadic colorectal cancer exhibit abnormal activation of the Wnt/β-catenin signaling due to mutation of the APC gene. We have generated Apc knockout murine models to increase our understanding of cancer development and progression. Our previous work has demonstrated that Apc loss is sufficient to initiate tumorigenesis. Now, we are searching critical Wnt/β-catenin downstream events that act as drivers for intestinal cancer.
Our recent work highlighted the activation of autophagy in human colon cancers and demonstrated that inhibition of autophagy effectively protect from tumor initiation and progression. Our data demonstrate that the loss of autophagy in the intestinal epithelial cell is responsible for an antitumor immune response and an alteration of the gut microbiota involved in the fight against tumor initiation. In addition, the loss of autophagy in cancer cells suppresses tumor progression via a metabolic stress and cell cycle arrest. Work in our lab continues to explore the significance of these signaling pathways in intestinal tumor biology.
Model summarizing key aspects of the antitumoral functions of intestinal epithelial autophagy inhibition in tumorigenesis mediated by Apc loss.