Flick the cancer stem cells’ switch to turn breast cancer off

Orateur : Christophe GINESTIER (CRCM, Marseille)

Tumor cell heterogeneity has been pointed out as the main cause of therapeutic failure. Tumor cell organization is a complex ecosystem where several subpopulations of cancer stem cells (CSCs) maintain the long-term oligoclonal architecture of the tumor. Deciphering the multiple factors that can influence intratumoral evolution is a prerequisite to understand therapeutic resistance, tumor progression, and local or distant recurrence. Recently, we identified miR-600 as a bimodal switcher that balances breast CSC-fate from a self-renewing to a differentiation state, with a direct impact on tumor progression. Our findings highlighted a miR-600/SCD1/WNT axis in which miR-600 regulates the produc1on of active lipid-modified WNT proteins. The clinical relevance of these observa+ons was shown in a series of breast tumors in which patients with miR-600-expressing tumors had a better clinical outcome than patients without miR-600 expression. Our study was the first to report a miRNA switcher in breast CSCs and it underlines the importance of identifying such master determinants of CSCfate to develop new clinical tools.

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