title: Reduced SLC27A2 induces cisplatin resistance in lung cancer stem cells by negatively regulating Bmi1-ABCG2 signaling.
abstract: Platinum-based chemotherapies have long been used as a standard treatment in non-small cell lung cancer (NSCLC). However, cisplatin resistance is a major problem that restricts the use of cisplatin. Lung cancer stem cells (LCSCs) represent a subpopulation that is responsible for chemo-resistance. We aim to investigate the biological function of SLC27A2 and its underlying mechanisms in regulating chemo-resistance to cisplatin in LCSCs. Here, our findings testified that CD166+cells which were derived from fresh primary NSCLC samples displayed stem cell-like features and were resistant to chemotherapy drug cisplatin. In patient cohort, we found the presence of a variable fraction of CD166+cells in 24 out of 25 primary NSCLC samples. Significantly, SLC27A2 expression was reduced in CD166+LCSCs. Reduced SLC27A2 correlated chemo-response and poor patient survival. Our results indicated that enhanced SLC27A2 expression sensitized CD166+LCSCs to cisplatin by in vitro and in vivo experiments. Microarray profiling showed that the expression of Bmi1 and ABCG2 was enhanced in p-SLC27A2-LCSCs compared with that in pc3.1DNA-LCSCs. Furthermore, we demonstrated that reduced SLC27A2 induced chemo-resistance in CD166+LCSCs by negatively regulating Bmi1-ABCG2 signaling, and ABCG2 was a direct transcriptional target of Bmi1. Thus, this study widens the window for identification and targeting of a cisplatin-resistant population and contributes to the development of potential therapeutics to improve the current treatment modalities in NSCLC. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Thoracic surgery, The Second People's Hospital of Anhui, Hefei 230000, Abhui Province, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Thoracic surgery, The Second People's Hospital of Anhui, Hefei 230000, Abhui Province, People's Republic of China.
authors.forename: Shifei
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Thoracic surgery, The Second People's Hospital of Anhui, Hefei 230000, Abhui Province, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Thoracic surgery, The Second People's Hospital of Anhui, Hefei 230000, Abhui Province, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qian
authors.affiliation: Department of Thoracic surgery, The Second People's Hospital of Anhui, Hefei 230000, Abhui Province, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Thoracic surgery, The Second People's Hospital of Anhui, Hefei 230000, Abhui Province, People's Republic of China. Doc_gt@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology; D003066:Coenzyme A Ligases / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005326:Fetal Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D063150:Polycomb Repressive Complex 1 / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D015703:Antigens, CD; D000970:Antineoplastic Agents; D015816:Cell Adhesion Molecules, Neuronal; D002945:Cisplatin; D003066:Coenzyme A Ligases; D005326:Fetal Proteins; D009363:Neoplasm Proteins; D063150:Polycomb Repressive Complex 1; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; C116614:ABCG2 protein, human; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C069077:BMI1 protein, human
keywords: ABCG2; Bmi1; CD166; SLC27A2; chemotherapeutic resistance; lung cancer stem cells