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Project

(Re)defining the origin and cellular niche of melanoma stem cells

It has been suggested that only a restricted number of cancer cells,
known as cancer stem cells (CSCs), are fated to fuel tumour growth.
As a result, these specialised cells have become the targets of
intense drug discovery efforts. In melanoma, however, whether
CSCs exist has remained unclear. Combining single-cell RNA
sequencing with in vivo lineage tracing and mathematical modelling,
we identified a population of melanoma cells that may function as
CSCs. We propose herein to firmly establish their functional
contribution to primary and metastatic growth using genetic lineage
tracing and ablation experiments.
Importantly, based on (our own) recent findings, we hypothesise, that
most, if not all, melanoma cells can acquire these “dangerous” CSC
properties when exposed to appropriate cues. We therefore also
propose to define the spatial distribution of this newly identified stem
cell population, map their cellular niche and identify intrinsic and
extrinsic mechanisms of tumour-stromal cell interactions that regulate
their identity and cell reprogramming ability (i.e. plasticity). We will
then test whether pharmacological interventions that target key
niche-dependent CSC specification mechanisms can restrict tumour
growth. This project will pave the way for the development of
innovative therapies that contend with, or even exploit, the
“chameleonic” behaviour of cancer cells.

Date:1 Jan 2022 →  Today
Keywords:Melanoma, Intra-tumor heterogeneity, Cancer stem cell
Disciplines:Cancer biology, Cancer diagnosis, Cancer therapy