title: Targeting PSG1 to enhance chemotherapeutic efficacy: new application for anti-coagulant the dicumarol.
abstract: Chemotherapeutic response is critical for the successful treatment and good prognosis in cancer patients. In this study, we analysed the gene expression profiles of preoperative samples from oestrogen receptor (ER)-negative breast cancer patients with different responses to taxane-anthracycline-based (TA-based) chemotherapy, and identified a group of genes that was predictive. Pregnancy specific beta-1-glycoprotein 1 (PSG1) played a central role within signalling pathways of these genes. Inhibiting PSG1 can effectively reduce chemoresistance via a transforming growth factor-β (TGF-β)-related pathway in ER-negative breast cancer cells. Drug screening then identified dicumarol (DCM) to target the PSG1 and inhibit chemoresistance to TA-based chemotherapy in vitro, in vivo, and in clinical samples. Taken together, this study highlights PSG1 as an important mediator of chemoresistance, whose effect could be diminished by DCM.
authors.affiliation: National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: He
authors.affiliation: Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300060, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Bioelectronics, Southeast University Sipailou 2#, Nanjing 210096, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Cellular and Molecular Pharmacology, School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Gu
authors.affiliation: Department of Cellular and Molecular Pharmacology, School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, China.
authors.forename: Chun-Xiao
authors.initials: CX
authors.lastname: Lu
authors.affiliation: Department of Cellular and Molecular Pharmacology, School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, China.
authors.forename: Ai-Qin
authors.initials: AQ
authors.lastname: Mao
authors.affiliation: National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Guang-Yuan
authors.initials: GY
authors.lastname: Zhang
authors.affiliation: National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Zhong-Yang
authors.initials: ZY
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Bioelectronics, Southeast University Sipailou 2#, Nanjing 210096, China.
authors.forename: Jin-Ke
authors.initials: JK
authors.lastname: Wang
authors.affiliation: State Key Lab of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China maxin@jiangnan.edu.cn fulijyb@hotmail.com) haojunjun@mail.kiz.ac.cn.
authors.forename: Jun-Jun
authors.initials: JJ
authors.lastname: Hao
authors.affiliation: Department of Breast Cancer Pathology and Research Laboratory, State Key Laboratory of Breast Cancer Research, Cancer Institute and Hospital, Tianjin Medical University, Tianjin 300060, China maxin@jiangnan.edu.cn fulijyb@hotmail.com) haojunjun@mail.kiz.ac.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Cellular and Molecular Pharmacology, School of Pharmaceutical Sciences, Jiangnan University, Wuxi 214122, China maxin@jiangnan.edu.cn fulijyb@hotmail.com) haojunjun@mail.kiz.ac.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D045744:Cell Line, Tumor; D001728:Dicumarol / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D011268:Pregnancy-Specific beta 1-Glycoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D043823:Taxoids / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D001952:Bridged-Ring Compounds; D011268:Pregnancy-Specific beta 1-Glycoproteins; D043823:Taxoids; D016212:Transforming Growth Factor beta; C080625:taxane; D001728:Dicumarol
keywords: chemoresistance; dicumarol; pregnancy specific beta-1-glycoprotein 1 (PSG1)