Opposing Regulation of Cancer Properties via KRT19-Mediated Differential Modulation of Wnt/β-Catenin/Notch Signaling in Breast and Colon Cancers.

Although Keratin 19 (KRT19) has been reported as a tumor cell marker and found to interact with other proteins that modulate cancer properties, its role in cancer prognosis remains to be fully elucidated. We found that expression was increased in both colon and breast cancer, but that knockdown of showed opposing effects on cancer properties. In colon cancer, knockdown resulted in suppression of cancer via downregulation of Wnt/Notch signaling without altering transcription. In breast cancer, knockdown led to an increase in cancer properties because of attenuated Wnt and enhanced Notch signaling. In colon cancer, KRT19 interacted with β-catenin but not with RAC1, allowing the LEF/TCF transcription factor to bind primarily to the and promoter regions, whereas in breast cancer, KRT19 interacted with the β-catenin/RAC1 complex and led to apparent upregulation of expression and NUMB-mediated suppression of Notch signaling. These results reveal a novel differential role of KRT19 in carcinogenesis, due to differential modulation of Wnt/β-catenin/Notch signaling crosstalk through various interactions of KRT19 with only β-catenin or with the β-catenin/RAC1 complex, which might have implications for clinical cancer research.