Fundamental & Translational Research

Deciphering a new mode of collective migration

Project leaders: Diane-Laure Pagès and Emmanuel Dornier

This project aims at decrypting a new mode of collective cell migration that we identified from cancer explants. This project addresses fundamental mechanistic questions on collective cell migration and we use micro-engineered devices to solve them. Our studies suggest that neoplastic programs favor this invasion strategy, therefore, unlocking the underlying mechanism may provide potential target to impede the metastatic dissemination of cancers in the future. 

Most of the migratory events orchestrating metazoan embryonic development and adult homeostasis are collective. Cohesive cell cohorts are driven by Leader cells exerting adhesion-mediated dragging forces. The scope of this project is to understand the fundamental mechanisms underlying this new mode of collective migration. The experiments aim at solving three important questions, in collaboration with biophysicists in microfluidic systems:

Our main questions:

  • How are forces generated in the cluster? 
  • How is the group coordinated?
  • Is there a leader/follower hierarchization in this mode of migration?

“Tumour Spheres with Inverted Polarity” in the metastatic spread of carcinomas

Project leaders: Maximiliano Gelli

Through the analysis of primary explants from large cohort of patients, we identified TSIPs (Tumour Spheres with Inverted Polarity) as the malignant tumour intermediates that initiate peritoneal metastases in patients with poor prognosis colorectal cancer (Zajac et al.). 

The scope of this project is to define the contour of TSIP-based dissemination considering primary tumour types and subtypes, dissemination routes and metastatic sites.

 

First, we want to determine whether TSIP-based dissemination is specific to this pathological condition or a generic mechanism that could mediate the metastatic spread of other primary cancers to different metastatic sites.

Second, we want to determine how TSIPs initially form, acquire and maintain their unique organization in the course of their dissemination.

 

We are focusing on the following:

  • Can TSIP mediate the dissemination of colorectal cancer to the liver, one of its main metastatic site?

 

  • Are TSIPs produced by primary tumor born in other anatomical sites? We will investigate carcinomas of different origins as well as their metastatic sites.

 

  • Do TSIP-producing cancers harbor common molecular traits?

Determine the processes of TSIP formation and polarity inversion

Project leaders: Joel Raingeaud, Jean-Baptiste Lopez and Charlotte Canet-Jourdan

TSIPs are malignant intermediates spreading the cancer in the body. It is essential to understand how tumors produce them if we want to interfere with this process. This multiscale investigates TSIPs biology at the molecule, cell and tissue levels.

  • What are the oncogenic drivers triggering the formation of TSIPs in the primary tumor? 
  • How does that translate into the cellular processes underlying the sprouting of TSIPs from the precursor lesion?
  • How do TSIPs maintain the apico-basolateral polarity inherited from their specific inverted topology?