Reprogramming breast cancer cells to breast cancer stem cells-like by the POU1F1 transcription factor

POU1F1 (also named PIT-1) is a well-known transcription factor involved in embryonic and adult pituitary development that has also been analyzed for its role in breast cancer . This study provides compelling evidence of POU1F1 in reprogramming breast cancer cells into BCSC-like. Our data demonstrates that POU1F1 induces a BCSC-like phenotype in breast tumor cells by deregulating markers such as CD24, CD44, CD133, and ALDH. These phenotypic modifications are correlated with functional changes, i.e. higher clonogenicity, increased mammospheres formation, and increased glycolysis metabolism. In addition, using in vivo immunodeficient mice models we found that a subpopulation of ALDHhigh cells from the POU1F1 overexpressing MCF-7 cells possess high tumor-initiating capacity, high resistance to chemo- and radiotherapy, and reduced overall survival. Mechanistically, POU1F1 induces an increase in IL-6 mRNA expression and raises IL-6 in the culture medium. This activates the IL-6/JAK/STAT3 pathway, which in turn increases ALDH mRNA expression. RNA-seq profiling of wildtype MCF-7 cells and their overexpreesion of POU1F1 transcripcion factor.