Rôles des protéines liant l'ARN et du métabolisme cellulaire dans la tumorigenèse et la progression tumorale

 

Marc-Étienne Huot

Centre hospitalier de l'Université de Montréal [CHUQ]

 

Domaine : cancer

Programme Chercheurs-boursiers - Junior 2

Concours 2018-2019

My laboratory investigates how mRNA-binding protein regulates metastatic dissemination (theme I) and cellular metabolism (theme II) during tumor progression.

Theme I: The RNA-based control of biological processes has always been overlooked in cancer progression and metastases formation. Within theme II, we directly address this omission. Our results strongly suggest that cancer-related dysregulation of RNA-binding protein activity, can affect cancer cell dissemination and alter tissue homing. Herein, we will determine how mRNA-binding proteins can affect cancer cell dissemination, a complex process by which cancer cells leave the primary tumor to colonize distant tissues to form secondary tumors (metastases). The proposed research will define how these RNA-binding proteins can modulate metastatic cells to recognize specific microenvironments from a specific tissue and determine if altering their RNA-binding activity can affect implantation site selection. This proposed research could offer new therapeutic strategies to block cancer progression, metastasis and thus increase patient survival.

Theme II: Cancer cells exploit basic metabolism differently than their normal counterparts. Herein, we will define two novel regulatory mechanisms affecting mTOR, a major regulator of cellular metabolism, often found to be constitutively activated in cancers. In the first part, we will define how mRNA-binding proteins can target specific sequence within non-coding regions of mTOR mRNA to regulate its splicing, stability, expression and thus, its activity. In the second portion of this theme, we will investigate a previously unsuspected link between metabolic defects and oncogenic activation of mTOR. This is mainly caused by mutations observed in more than 70% of low-grade brain cancer. This recently identified mechanism modulating mTOR activity represent an important event in brain tumor formation and progression. Elucidating the oncogenic activities of these mechanisms will allow the development of novel targeted and personalized therapies for deadly brain cancers.