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

Concepcion, L. A.; Ruzo, S. S.; Gonzalez, S. R.; Gois, M.; Arias, M. E.; Delgado, D. M.; Lado, N.; Caballero, T. G.; Aguiar, P.; Fernandez, R. P.

doi:10.1101/2025.04.30.651395

bioRxiv · 10.1101/2025.04.30.651395

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

Concepcion, L. A.·Ruzo, S. S.·Gonzalez, S. R.·Gois, M.·Arias, M. E.·Delgado, D. M.·Lado, N.·Caballero, T. G.·Aguiar, P.·Fernandez, R. P.

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Abstract

Breast cancer stem cells (BCSCs) have been proposed as the cause of resistance to conventional treatments and as the origin of breast cancer recurrence and metastasis. However, BCSC origin is not fully understood. Using breast cancer cell lines with POU1F1 overexpression and knockdown as well as immunodeficient mice models, this study provides compelling evidence of the role of POU1F1 in reprogramming breast cancer cells into BCSC-like by deregulating CD24, CD44, CD133, and ALDH markers. In addition, a subpopulation from POU1F1 overexpressing MCF-7 cells with high levels of ALDH present functional changes, e.g., higher invasion, glycolytic metabolism, increased clonogenicity and mammosphere formation, high tumor-initiating capacity, and resistance to treatment. Mechanistically, these features seem to be mediated by POU1F1 activation of the IL-6/JAK2/STAT3 pathway. Our data suggests that hormone therapy-resistant Luminal A breast tumors with high levels of POU1F1 could be targeted by blocking the IL-6/JAK2/STAT3 pathway.

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Concepcion, L. A., Ruzo, S. S., Gonzalez, S. R., Gois, M., Arias, M. E., Delgado, D. M., Lado, N., Caballero, T. G., Aguiar, P., Fernandez, R. P.. 2025-05-04. Reprogramming breast cancer cells to breast cancer stem cell-like by the POU1F1 transcription factor. https://doi.org/10.1101/2025.04.30.651395

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