Cancer Stem Cells and the Slow Cycling Phenotype: How to Cut the Gordian Knot Driving Resistance to Therapy in Melanoma

Cancers
Luigi FattoreGennaro Ciliberto

Abstract

Cancer stem cells (CSCs) have historically been defined as slow cycling elements that are able to differentiate into mature cells but without dedifferentiation in the opposite direction. Thanks to advances in genomic and non-genomic technologies, the CSC theory has more recently been reconsidered in a dynamic manner according to a "phenotype switching" plastic model. Transcriptional reprogramming rewires this plasticity and enables heterogeneous tumors to influence cancer progression and to adapt themselves to drug exposure by selecting a subpopulation of slow cycling cells, similar in nature to the originally defined CSCs. This model has been conceptualized for malignant melanoma tailored to explain resistance to target therapies. Here, we conducted a bioinformatics analysis of available data directed to the identification of the molecular pathways sustaining slow cycling melanoma stem cells. Using this approach, we identified a signature of 25 genes that were assigned to four major clusters, namely 1) kinases and metabolic changes, 2) melanoma-associated proteins, 3) Hippo pathway and 4) slow cycling/CSCs factors. Furthermore, we show how a protein-protein interaction network may be the main driver of these melanoma cell subp...Continue Reading

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Citations

Apr 24, 2021·Frontiers in Oncology·Thahomina Khan, Horacio Cabral
Jun 29, 2021·Frontiers in Oncology·Claudia TrojanielloPaolo A Ascierto

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Methods Mentioned

BETA
sc-RNAseq
RNA-Seq

Software Mentioned

cBioPortal
RSEM
MSCsign
OncoPrint
GEPIA
UALCAN

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