Transcriptional Profiling of Tumorspheres Reveals TRPM4 as a Novel Stemness Regulator in Breast Cancer

Cancer stem cells (CSCs) have been implicated in the development of chemoresistance, tumor recurrence and metastasis in breast cancer, thus emerging as a promising target for novel therapies. To identify novel stemness regulators that could potentially be targeted in luminal ER+ tumors, we performed RNA-sequencing (RNA-seq) in MCF-7 adherent monolayer cells and tumorspheres enriched in breast CSCs (bCSCs). We identified 1421 differentially expressed genes (DEGs), with 923 of them being upregulated and 498 downregulated in tumorspheres. Gene ontology and pathway enrichment analyses revealed that distinct gene networks underlie the biology of the two cell systems. We selected the transient receptor potential cation channel subfamily M member 4 (TRPM4) gene that had not been associated with cancer stemness before for further investigation. We confirmed that TRPM4 was overexpressed in tumorspheres and showed that its knock-down affected the stemness properties of bCSCs in vitro. TRPM4 inhibition revealed potential anti-tumor effects by directly targeting the bCSC subpopulation. We suggest that TRPM4 plays a key role in stemness mediation, and its inhibition may represent a novel therapeutic modality against bCSCs contributing in the improvement of breast cancer treatments.

Automated summary

Cancer stem cells play a significant role in chemoresistance, tumor recurrence, and metastasis in breast cancer, making them a promising target for new therapies. Through RNA-sequencing, researchers identified differential gene expression patterns between breast CSCs and non-CSCs, with the TRPM4 gene being found to be overexpressed in tumorspheres and affecting stemness properties. Inhibiting TRPM4 showed potential anti-tumor effects by targeting the bCSC subpopulation, suggesting a novel therapeutic approach for improving breast cancer treatments.