Cytokeratin 19 has a Role in the Reprogramming of Cancer Stem Cell-Like Cells to Less Aggressive and More Drug-Sensitive Cells.

Cytokeratin 19 () is a cytoplasmic intermediate filament protein, which is responsible for structural rigidity and multipurpose scaffolds. In several cancers, is overexpressed and may play a crucial role in tumorigenic transformation. In our previous study, we revealed the role of as signaling component which mediated Wnt/NOTCH crosstalk through NUMB transcription in breast cancer. Here, we investigated the function of in cancer reprogramming and drug resistance in breast cancer cells. We found that expression of was attenuated in several patients-derived breast cancer tissues and patients with a low expression of were significantly correlated with poor prognosis in breast cancer patients. Consistently, highly aggressive and drug-resistant breast cancer patient-derived cancer stem cell-like cells (konkuk university-cancer stem cell-like cell (KU-CSLCs)) displayed higher expression of cancer stem cell (CSC) markers, including , , and , but a much lower expression of than that is seen in highly aggressive triple negative breast cancer MDA-MB231 cells. Moreover, we revealed that the knockdown of in MDA-MB231 cells led to an enhancement of cancer properties, such as cell proliferation, sphere formation, migration, and drug resistance, while the overexpression of in KU-CSLCs resulted in the significant attenuation of cancer properties. regulated cancer stem cell reprogramming by modulating the expression of cancer stem cell markers (, , and ), as well as the phosphorylation of Src and GSK3β (Tyr216). Therefore, our data may imply that the modulation of expression could be involved in cancer stem cell reprogramming and drug sensitivity, which might have clinical implications for cancer or cancer stem cell treatment.