Endocytosis, cytoskeleton and cell migration
This group belongs to the UMR 1279 - Tumor cell dynamics
The overall objective of our lab is to understand how the mechanical properties of the tumoral environment influence cancer cell migration.
Our projects aim to understand the functions of clathrin-coated structures (CCSs) associated with changing physical parameters of the tumour environment. CCSs recruit surface receptors and package them in vesicles that bud into the cytosol. This endocytosis allows the absorption of nutrients but also the control of signalling pathways triggered by the receptors. As a result, the deregulation of endocytosis has been linked to many pathological situations, including cancers.
The development of tumours is accompanied by changes in the mechanical characteristics of tissues. In addition, when cancer cells escape the primary tumor, they migrate into an environment with unique 3D topological characteristics. However, it is not known how the physical parameters of the microenvironment affect CCSs and what the consequences are for cancer cells. Our published and preliminary work indicates that substrate stiffness (which is increased in tumour tissues) and environmental topology (when composed of fibres) may prevent CCSs from budding and achieving endocytosis. This frustration modulates the functions of CCSs, which then act as signalling platforms or adhesive structures and even as cues deposited behind migrating cells that define a road for the migration of following cells.
We are studying how frustrated CCSs help cancer-associated fibroblasts to migrate towards rigid substrates and how they create pathways for cancer cell migration. We are also studying how the topology of the microenvironment modulates the dynamics and functions of CCSs in cancer cells by regulating the adjustment of membrane tension and how this affects cancer cell migration in complex environments.