Thank you to @frm-officiel.bsky.social for supporting the 4th year of my PhD, and @cnrsbiologie.bsky.social, @inserm.fr, @unistra.fr, @fondationarc.bsky.social for supporting this project. @igbmc.bsky.social

A great heartfelt thank you to the people who mentored and guided me through this project @metzgerlab.bsky.social @gilleslaverny.bsky.social and @beatrizgerman.bsky.social and to our great collaborators @sandrine-henri.bsky.social and Le Magnen lab.

Altogether, we uncovered that prostate tumor heterogeneity and plasticity might arise early during tumorigenesis in a localized manner as a result of bidirectional communication between cancer cells and their microenvironment. Targeting these interactions might limit cancer progression.

Importantly, we found that our EMT cell population transcriptomic profile is similar to that of MSPC described by Han and colleagues doi.org/10.1016/j.ce... and might arise in other intraductal prostate tumors rdcu.be/d7yLi

Using organoid cultures, we validated that IL6 produced by CAFs is sufficient and necessary to induce EMT-like phenotype in PTEN- and p53-deficient tumor cells.

Our single-cell analyses identified a novel luminal cell population with EMT and cell plasticity characteristics that was driven by Stat3 signaling and we identified CAFs as sources of IL6 that would induce Stat3 in tumor cells.

To answer this, we used genetically-engineered mouse models that presented heterogeneous tumor development: while some presented intraductal and invasive tumors, others additionally developed hepatic micrometastases.

In this study, we wanted to address the question of what drives the heterogeneity of prostate tumor progression in PTEN- and p53-deficient tumors, and especially, how such tumors progress to metastases, the leading cause of prostate-cancer related deaths.