Department of Pharmacology and Chemical Biology

Killing breast tumor-initiating cellĀ  by synergizing molecular axes of PARP-KLF4 and EGFR-KLF4


PARP1, ionizing irradiation and EGF receptor signaling profoundly promote renewal of tumor-initiating cells. Synergistic blockade of PARP1-KLF4 and EGFR-KLF4 cascade could efficiently kill breast cancer cells. One of the most recent striking findings in stem cell and tumor-initiating cell field is that PARP1 could elevate iPS induction-rate by 100 folds, while ionizing irradiation significantly enhances subpopulation of breast tumor-initiating cell resulting in increases in cancer heterogeneity. We and others have observed that KLF4 is an important factor that facilitates the effect of PARP1 and ionizing irradiation. In addition, we also observed EGF2 is critical to alter subpopulation of breast tumor-initiating cell. Accordingly, we are now addressing the mechanism of how PARP1, ionizing irradiation and EGFR synergistically orchestrate KLF4 resulting in increased breast tumor-initiating cell population, and we are therefore proposing a synthetic lethality based strategy to treat breast tumor-initiating cell using combination of PARP1 and EGF2 inhibitors in human breast cancer xenograft mouse model.