title: Transforming growth factor β-activated kinase 1 inhibitor suppresses the proliferation in triple-negative breast cancer through TGF-β/TGFR pathway.
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.
authors.affiliation: Department of Oncology, Daqing Oil Field General Hospital, Daqing City, China.
authors.forename: Liangyu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Breast surgery, Tianjin Central Obstetrics and Gynecology Hospital, Tianjin City, China.
authors.forename: Zelong
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Yale Stem Cell Center, Yale University, New Haven, CT, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Daqing Oil Field General Hospital, Daqing City, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Tang
authors.affiliation: Yale Stem Cell Center, Yale University, New Haven, CT, USA.
authors.forename: Jiesi
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Oncology, Daqing Oil Field General Hospital, Daqing City, China.
authors.forename: Dehui
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Daqing Oil Field General Hospital, Daqing City, China.
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Zhiyang
authors.identifier: http://orcid.org/0000-0002-8391-1904
authors.initials: Z
authors.lastname: Han
authors.affiliation: Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Yale Stem Cell Center, Yale University, New Haven, CT, USA.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Yin
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D015025:Zearalenone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology / Q000008:administration & dosage; D000099151:MAP Kinase Kinase Kinase 7; D007783:Lactones; D012118:Resorcinols
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D020930:MAP Kinase Kinase Kinases; D047428:Protein Kinase Inhibitors; D016212:Transforming Growth Factor beta; D015025:Zearalenone; D000099151:MAP Kinase Kinase Kinase 7; C505734:7-oxozeanol; D007783:Lactones; D012118:Resorcinols
keywords: 5Z-7-Oxozeaenol; Transforming growth factor β-activated kinase 1; cell proliferation; triple-negative breast cancer