Journal
CANCERS
Volume 11, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/cancers11010099
Keywords
KRT19; Wnt/beta-catenin; NUMB crosstalk; Notch pathway; colon cancer; breast cancer
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Funding
- National Research Foundation (NRF) of the Korean government [2015R1A5A1009701]
- KU Research Professor Program of Konkuk University
- National Research Foundation of Korea [2015R1A5A1009701] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 KRT19 expression was increased in both colon and breast cancer, but that knockdown of KRT19 showed opposing effects on cancer properties. In colon cancer, KRT19 knockdown resulted in suppression of cancer via downregulation of Wnt/Notch signaling without altering NUMB transcription. In breast cancer, KRT19 knockdown led to an increase in cancer properties because of attenuated Wnt and enhanced Notch signaling. In colon cancer, KRT19 interacted with beta-catenin but not with RAC1, allowing the LEF/TCF transcription factor to bind primarily to the LEF1 and TCF7 promoter regions, whereas in breast cancer, KRT19 interacted with the beta-catenin/RAC1 complex and led to apparent upregulation of NUMB 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/beta-catenin/Notch signaling crosstalk through various interactions of KRT19 with only beta-catenin or with the beta-catenin/RAC1 complex, which might have implications for clinical cancer research.
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