title: The ROS-mediated activation of STAT-3/VEGF signaling is involved in the 27-hydroxycholesterol-induced angiogenesis in human breast cancer cells.
abstract: Breast cancer (BC) is the leading cause of cancer-related mortality among females worldwide, and angiogenesis plays a crucial role in BC progression. 27-Hydroxycholesterol (27HC) is an endogenous selective estrogen receptor modulator, which promotes the growth and metastasis of BC. Here, we further found that, 27HC improved the angiogenic ability of BC in a VEGF-dependent manner. For the molecular mechanisms, on one hand, as an estrogen-like factor, 27HC enhanced the expression of VEGF by the classical ERα/VEGF signaling in ER-positive BC cells; on the other hand, in both ER-positive and ER-negative BC cells, 27HC enhanced the generation of ROS, which in turn activated the STAT-3/VEGF signaling in an ER independent manner. Either blocking the generation of ROS or knockdown of STAT-3 attenuated the 27HC-induced autocrine of VEGF and angiogenesis. These findings not only suggested a mechanism whereby 27HC enhanced the angiogenesis, but also helped to recognize the 27HC as a novel potential harmful factor in BC, especially in the menopause 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: 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: 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: 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: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D019898:Autocrine Communication / Q000187:drug effects; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000187:drug effects; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D006888:Hydroxycholesterols / Q000633:toxicity*; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000187:drug effects / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000378:metabolism*
chemical_list: D043925:Angiogenesis Inducing Agents; D047628:Estrogen Receptor alpha; D006888:Hydroxycholesterols; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020845:Selective Estrogen Receptor Modulators; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C076996:27-hydroxycholesterol
keywords: 27-Hydroxycholesterol; Angiogenesis; Breast cancer; Reactive oxygen species; Signal transducer and activator of transcription 3