Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B

• DOI: 10.1038/s41590-022-01290-3
• Publication Date: 2022-08-24T16:04:14Z
• Authors: Martina Musella; Andrea Guarracino; Nicoletta Manduca; Claudia Galassi; Eliana Ruggiero; Alessia Potenza; Ester Maccafeo; Gwenola Manic; Luca Mattiello; Sara Soliman Abde...; Michele Signore; Marco Pietrosanto; Manuela Helmer-Ci...; Matteo Pallocca; Maurizio Fanciulli; Tiziana Bruno; Francesca De Nicola; Giacomo Corleone; Anna Di Benedetto; Cristiana Ercolani; Edoardo Pescarmona; Laura Pizzuti; Francesco Guidi; Francesca Sperati; Sara Vitale; Daniele Macchia; Massimo Spada; Giovanna Schiavoni; Fabrizio Mattei; Adele De Ninno; Luca Businaro; Valeria Lucarini; Laura Bracci; Eleonora Aricò; Giovanna Ziccheddu; Francesco Facchiano; Stefania Rossi; Massimo Sanchez; Alessandra Boe; Mauro Biffoni; Ruggero De Maria; Ilio Vitale; Antonella Sistigu
• Keywords: Reprogramming

Cancer stem cells (CSCs) are a subpopulation of cancer endowed with high tumorigenic, chemoresistant and metastatic potential. Nongenetic mechanisms acquired resistance increasingly being discovered, but molecular insights into the evolutionary process CSCs limited. Here, we show that type I interferons (IFNs-I) function as hubs during immunogenic chemotherapy, triggering epigenetic regulator demethylase 1B (KDM1B) to promote an adaptive, yet reversible, transcriptional rewiring towards stemness immune escape. Accordingly, KDM1B inhibition prevents appearance IFN-I-induced CSCs, both in vitro vivo. Notably, heterogeneous terms multidrug resistance, plasticity, invasiveness immunogenicity. Moreover, breast (BC) patients receiving anthracycline-based positively correlated CSC signatures. Our study identifies IFN-I → axis potent engine cell reprogramming, supporting targeting attractive adjunctive drugs prevent expansion increase long-term benefit therapy.