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Chem Biol Drug Des. 2017 Sep;90(3):450-455. doi: 10.1111/cbdd.12965. Epub 2017 Apr 11.

Transforming growth factor β-activated kinase 1 inhibitor suppresses the proliferation in triple-negative breast cancer through TGF-β/TGFR pathway.

Author information

1
Department of Oncology, Daqing Oil Field General Hospital, Daqing City, China.
2
Department of Breast surgery, Tianjin Central Obstetrics and Gynecology Hospital, Tianjin City, China.
3
Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.
4
Yale Stem Cell Center, Yale University, New Haven, CT, USA.
5
Department of Neurosurgery, Daqing Oil Field General Hospital, Daqing City, China.
6
Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Abstract

Breast cancer is one of the most invasive cancer types in female population. The functional activity of Transforming growth factor β-activated kinase 1 (TAK1) in breast cancer progression increasingly attracts attention as it provides a potential target for antibreast cancer drug development. However, the fundamental role of TAK1 for triple-negative breast cancer (TNBC) progression and the effect of potential anti-TAK1 drug candidate needs to be further evaluated. Herein, we focused on the role of TAK1 in human breast cancer cells, and we hypothesized that the inhibition of TAK1 activation can repress the growth of human TNBC cells. We found that the TAK1 is robustly activated within cancer cell population of clinic-derived TNBC samples and the human breast cancer cell lines in culture. Furthermore, we determined the effect of 5Z-7-oxozeaenol (5Z-O), a TAK1-specific small molecule inhibitor, on proliferation of human TNBC cell line. 5Z-O treatment significantly suppressed the proliferation of human TNBC cells. Collectively, these demonstrate the role of TAK1 in human breast cancer and the antiproliferate effect of TAK1 inhibitor. Our study sets the stage for further research on TAK1 as a promising target for development of anti-TNBC drugs and therapeutic strategies.

KEYWORDS:

5Z-7-Oxozeaenol; Transforming growth factor β-activated kinase 1; cell proliferation; triple-negative breast cancer

PMID:
28224764
DOI:
10.1111/cbdd.12965
[Indexed for MEDLINE]
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