title: The effects and mechanisms of SLC34A2 on tumorigenicity in human non-small cell lung cancer stem cells.
abstract: A novel paradigm in tumor biology suggests that non-small cell lung cancer (NSCLC) growth is driven by lung cancer stem cell-like cells (LCSCs), but molecular mechanisms regulating tumorigenic and self-renewal potential of LCSCs are still unclear. Here, we aim to investigate biological function of SLC34A2 in regulating tumorigenicity of LCSCs and its underlying mechanisms. Our findings testified that CD166(+) cells which were derived from fresh primary NSCLC samples displayed stem cell-like features. Fluorescence-activated cell sorting (FACS) analysis showed the presence of a variable fraction of CD166 cells in 15 out of 15 NSCLC samples. Significantly, CD166(+) LCSCs from primary NSCLC tumors expressed high level of SLC34A2 which was required for CD166(+) LCSCs tumorigenic and self-renewal potential. In NSCLC patient cohort, increased SLC34A2 expression correlated with histology, which suggests a potential role of SLC34A2 in CD166(+) LCSCs. Furthermore, Wnt/β-catenin pathway and Bmi1 were found necessary for tumorigenicity and self-renewal capacity of CD166(+) LCSCs by a series in vitro and in vivo experiments. Then, our study indicated that SLC34A2 regulated Bmi1 to promote tumorigenic and self-renewal potential of CD166(+) LCSCs through Wnt/β-catenin pathway. In this study, the characterization of molecular basis of SLC34A2 in CD166(+) LCSCs not only allows for better understanding of the mechanisms regulating tumorigenicity of this specific population of NSCLC cells but also provides insight into the gradual improvement of more effective cancer therapies against this disease.
authors: Department of Chest Cardiac, the First Hospital of Yulin City, NO.93, Yulin avenue, Gaoxin zone, Yulin, 719000, Shaanxi Province, People's Republic of China.
authors: Zhanxin
authors: Z
authors: Jiang
authors: Department of Chest Cardiac, the First Hospital of Yulin City, NO.93, Yulin avenue, Gaoxin zone, Yulin, 719000, Shaanxi Province, People's Republic of China.
authors: Yanhong
authors: Y
authors: Hao
authors: Department of Chest Cardiac, the First Hospital of Yulin City, NO.93, Yulin avenue, Gaoxin zone, Yulin, 719000, Shaanxi Province, People's Republic of China.
authors: Xiaoquan
authors: X
authors: Ding
authors: Department of Chest Cardiac, the First Hospital of Yulin City, NO.93, Yulin avenue, Gaoxin zone, Yulin, 719000, Shaanxi Province, People's Republic of China.
authors: Zhibin
authors: Z
authors: Zhang
authors: Department of Chest Cardiac, the First Hospital of Yulin City, NO.93, Yulin avenue, Gaoxin zone, Yulin, 719000, Shaanxi Province, People's Republic of China.
authors: Peng
authors: P
authors: Liu
authors: Department of Chest Cardiac, the First Hospital of Yulin City, NO.93, Yulin avenue, Gaoxin zone, Yulin, 719000, Shaanxi Province, People's Republic of China.
authors: Xueqiang
authors: X
authors: Wei
authors: Department of Chest Cardiac, the First Hospital of Yulin City, NO.93, Yulin avenue, Gaoxin zone, Yulin, 719000, Shaanxi Province, People's Republic of China. xijunfeng_123@163.com.
authors: Junfeng
authors: J
authors: Xi
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology
chemical_list: C493557:SLC34A2 protein, human; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; C481581:MAPK7 protein, human; D048054:Mitogen-Activated Protein Kinase 7
keywords: Bmi1; CD166; Lung cancer stem cells; SLC34A2; Tumorigenicity; Wnt/β-catenin pathway