title: Enhancement of vascular endothelial growth factor release in long-term drug-treated breast cancer via transient receptor potential channel 5-Ca(2+)-hypoxia-inducible factor 1α pathway.
abstract: Chemotherapy targeting anti-angiogenesis in tumors may have insufficient efficacy, but little is known about the underlying mechanisms. Here, we showed that the Ca(2+)-permeable channel, TrpC5, is highly expressed in human breast cancer after long-term chemotherapy drug-treatment. It mediates downstream hypoxia-inducible factor 1α accumulation in the nucleus, and then activates the transcription of vascular endothelial growth factor which promotes tumor angiogenesis, leading to a poor chemotherapeutic outcome. We verified this mechanism at both the cellular and xenograft levels. Moreover, in samples from patients, high TrpC5 expression was correlated with enhanced tumor vasculature after chemotherapy. Taken together, our research demonstrated the essential role of TrpC5 in tumor angiogenesis when facing the challenge of chemotherapy and presents a new potential target for overcoming the high vasculature of human breast cancer after chemotherapy.
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors.forename: Qiongxi
authors.initials: Q
authors.lastname: Pan
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Meng
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors.forename: Yueshui
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China.
authors.forename: Aiqin
authors.initials: A
authors.lastname: Mao
authors.affiliation: Affiliated Hospital, Jiangnan University, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Affiliated Hospital, Jiangnan University, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yao
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China. Electronic address: jinjian31@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, China. Electronic address: maxin@jiangnan.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D050052:TRPC Cation Channels; C491780:TRPC5 protein, human; D042461:Vascular Endothelial Growth Factor A; D004317:Doxorubicin
keywords: Adriamycin (PubChem CID: 31703); Breast cancer; Hypoxia-inducible factor (HIF); Long-term drug treatment; Transient receptor potential channel 5 (TrpC5); Vascular endothelial growth factor (VEGF)