title: 27-Hydroxycholesterol induces invasion and migration of breast cancer cells by increasing MMP9 and generating EMT through activation of STAT-3.
abstract: Breast carcinoma plays a vital role in the reasons of global women's death. ER-related invasion and migration play an important part in the development and prognosis of breast cancer. Here, we found that 27-Hydroxycholesterol (27HC) could induce epithelial-mesenchymal transition (EMT) and increase the expression of the matrix metalloproteinase 9 (MMP9) at mRNA level and the active form. Meanwhile, interestingly, we found 27HC activated signal transducer and activator of transcription 3 (STAT-3) in ER positive cells except activation of ER signaling. Furthermore, inhibition of STAT-3 by siRNA attenuated the 27HC-induced improvement of MMP9 and decreased the invasion and migration ability in MCF7 and T47D cells. In addition, 27HC could also promote MMP9, vimentin and active STAT-3 in the ER negative cells MDA-MB-231. All these results not only raise a mechanism whereby 27HC enhances the invasion and metastasis, but also is helpful to realize 27HC as a potential endogenous detrimental factor in breast tumor patients.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: lz-ny@njmu.edu.cn.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: liyuan@njmu.edu.cn.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism / Q000633:toxicity*; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D060888:Real-Time Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014162:Transfection
chemical_list: D006888:Hydroxycholesterols; D011960:Receptors, Estrogen; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C076996:27-hydroxycholesterol; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: 27-Hydroxycholesterol; Breast cancer; Epithelial-mesenchymal transition; Invasion and migration; Matrix metalloproteinase 9; Signal transducer and activator of transcription 3