NARILIS lunch seminar | Nordin BANSACCAL, ULB, Laboratory of Stem Cells and Cancer

We are pleased to invite you to a seminar given by

Dr. Nordin Bansaccal, MD

Université Libre de Bruxelles (ULB)

His seminar is entitled:

"ECM composition dictates cell competition and the regional competence for tumour initiation"

The skin epidermis is constantly renewed throughout life. Disruption of the balance between renewal and differentiation can lead to uncontrolled growth and tumour initiation. However, the ways in which oncogenic mutations impact the balance between renewal and differentiation and lead to clonal expansion, cell competition, tissue colonization and tumour development is currently unknown. Here, using multidisciplinary approaches combining in vivo clonal analysis using intra-vital microscopy, single cell analysis, and functional analysis, we defined, at a single cell resolution in living animals, how SmoM2 mutation that induces basal cell carcinoma (BCC) development, the most frequent cancer in human,  affects clonal competition and tumour initiation in real time.  We found that SmoM2 expression in the ear epidermis induced clonal expansion accompanied with tumour initiation and invasion. In contrast, SmoM2 expression in the back skin epidermis led to clonal expansion that induced lateral cell competition without inducing dermal invasion and tumour formation. Single cell analysis showed that oncogene expression is associated with a cellular reprogramming of adult interfollicular cells into embryonic hair follicle progenitor (EHFP) state in the ear but not in the back skin. Comparison between ear and back skin revealed a very different composition of the dermis with increased stiffness and a denser Collagen 1 network in the back skin. Decreasing Collagen, I expression in the back skin by collagenase, during natural ageing or following chronic UV exposure overcome the natural resistance of back skin basal cells to undergo EHFP reprogramming and tumour initiation following SmoM2 expression. Altogether our study demonstrates that ECM composition regulates the regional competence to undergo tumour initiation and invasion.

Publication in Nature: Bansaccal et al., 2023

Invited by Prof. Yves Poumay, UNamur, URPhyM