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Essential role of Notch4/STAT3 signaling in epithelial-mesenchymal transition of tamoxifen-resistant human breast cancer

Title
Essential role of Notch4/STAT3 signaling in epithelial-mesenchymal transition of tamoxifen-resistant human breast cancer
Author
김영미
Keywords
Tamoxifen resistance; Breast cancer; Metastasis; Notch4; STAT3; GROWTH-FACTOR RECEPTOR; STEM-CELL ACTIVITY; SERINE PHOSPHORYLATION; CROSS-TALK; STAT3; NOTCH; TRANSCRIPTION; ACTIVATION; EXPRESSION; INVASION
Issue Date
2017-04
Publisher
ELSEVIER IRELAND LTD
Citation
CANCER LETTERS, v. 390, Page. 115-125
Abstract
We previously demonstrated that tamoxifen (TAM)-resistant human breast cancer (TAMR-MCF-7) cells showed increased expression of mesenchymal marker proteins compared to the parent MCF-7 cells. Notch is functionally important in the promotion of epithelial mesenchymal transition (EMT) during both development and tumor progression. Notchl and Notch4 have been reported as prognostic markers in human breast cancer. Here, we indicated that Notch4, but not Notchl, plays a critical role in the regulation of EMT signaling in TAMR-MCF-7 cells. Notch4 suppression by either Notch inhibitors or Notch4 siRNA attenuated EMT signaling. Tyrosine-phosphorylated STAT3 protein is known as a crucial signaling molecule in the regulation of tumorigenesis and metastasis. We found that TAMR-MCF-7 cells exhibited constitutive STAT3 phosphorylation, and Notch inhibition reduced the level of activated STAT3 in TAMR-MCF-7 cells. An intrasplenic injection model of liver metastases was performed using TAMRMCF-7 cells. Mice injected with N-[N-(3,5-Difluorophenacety1)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT, 10 mg/kg) formed smaller splenic tumors and showed a reduced micrometastatic tumor burden in their livers compared with the control group treated with vehicle. To conclude, Notch4 could be a potential target to prevent metastasis in TAM -resistant breast cancer. (C) 2017 Elsevier B.V. All rights reserved.
URI
https://www.cancerletters.info/article/S0304-3835(17)30037-X/fulltexthttp://repository.hanyang.ac.kr/handle/20.500.11754/72021
ISSN
0304-3835; 1872-7980
DOI
10.1016/j.canlet.2017.01.014
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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