Interferon-beta represses cancer stem cell properties in triple-negative breast cancer

Abstract

SignificanceCurrent cancer therapies fail to repress tumor recurrence and metastasis in triple-negative breast cancer (TNBC) because they fail to target cells that possess epithelial–mesenchymal (E-M) plasticity and acquire cancer stem cell (CSC) properties. Identifying and engaging signaling pathways that regulate E-M/CSC plasticity within TNBC therefore remains an unmet critical clinical need. Recent evidence demonstrates that presence of E-M/CSC plasticity in TNBC correlates with a repressed interferon/STAT gene signature. Our data demonstrate that exogenous IFN-β targets and represses E-M/CSC plasticity by reengaging type I IFN signaling in CSC. Our findings have clinical relevance, as IFN-β signaling correlates with improved patient survival and repressed CSC in TNBC. Thus, our work suggests a therapeutic use for IFN-β in the repression of E-M/CSC–driven tumor recurrence and metastasis in TNBC.

Concise Review: Targeting Cancer Stem Cells and Their Supporting Niche Using Oncolytic Viruses

“…Consistent with this, there are several published reports of synergy between OVs and other therapeutic modalities . Interestingly, IFN‐I signaling represses CSC properties in triple‐negative breast cancer (TNBC), with IFN‐β being proposed as a potential treatment option for TNBC . The latter study demonstrated an inverse correlation between the CSC phenotype and IFN signaling, in line with a recent study showing breast CSCs were more prevalent in spontaneous tumors arising from IFN‐I signaling deficient mice .…”

Type I Interferons and Cancer: An Evolving Story Demanding Novel Clinical Applications

“…The involvement of IFN-I in the restraint of CSC was also recently reported by our group and others in breast cancer models [7,39,40]. In Her2/Neu transgenic mice, an impaired IFN-I signaling resulted in an increased amount of breast CSC during spontaneous carcinogenesis.…”

The Interactions Between Cancer Stem Cells and the Innate Interferon Signaling Pathway

“…These results clearly propose IFN-I as a negative regulator of stemness in breast cancer tumor cells. Accordingly, Doherty et al (144) obtained similar conclusions when studying the role of IFN-β on triple-negative breast cancer (TNBC) CSCs, using an in vitro model of primary human mammary epithelial cells (HMEC) virally transduced with transforming factors. Within transformed cells, a subpopulation of mesenchymal-like cells with CSCs properties emerged (Mes/CSC), while the remaining cells maintained an epithelial phenotype and did not present such properties (Ep/non-CSC).…”