title: The effects and mechanisms of SLC34A2 in tumorigenesis and progression of human non-small cell lung cancer.
abstract: BACKGROUND
  SLC34A2 with highest expressions in lung, small intestine and kidney encoded a type 2b sodium-dependent phosphate transporter (NaPi-IIb). In lung, SLC34A2 only expressed in the apical membrane of type II alveolar epithelium cells (ATII cells) and played a pivotal role during the fetal lung development and embryonic development. ATII cells acting as multifunctional stem cells might transform into NSCLC after undergoing exogenous or endogenous factors. Increasing evidences showed that the genes performing critical roles during embryogenesis were also expressed during the development of cancer. In addition, recent research found the expression of SLC34A2 had a significant difference between the surgical samples of NSCLC and normal tissues, and SLC34A2 was down-regulated in lung adenocarcinoma cell line A549 and up-regulation expression of SLC34A2 could significantly inhibit cell viability and invasion of A549 in vitro. These results suggested SLC34A2 might play an important role in the development of NSCLC. However, the role of SLC34A2 in tumorigenesis and progression of NSCLC remains unknown.
  
  
  RESULTS
  Our study found that SLC34A2 was also significantly down-regulated in 14/15 of examined NSCLC tissues. Moreover, we found that expressions of SLC34A2 were reduced in six NSCLC cell lines for the first time. Our result also revealed a dramatic inhibitory effects of SLC34A2 on cell growth, migration and invasion of several NSCLC cell lines. SLC34A2 also strongly inhibited tumor growth and metastasis ability in A549 subcutaneous tumor model and lung metastasis model, respectively. Further studies found that the suppressive effects of SLC34A2 on tumorigenesis and progression might be associated with the down-regulation of related protein in PI3K/Akt and Ras/Raf/MEK signal pathway.
  
  
  CONCLUSIONS
  For the first time, our data indicated that SLC34A2 could exert significantly suppressive effects on tumorigenesis and progression of NSCLC. SLC34A2 might provide new insights for further understanding the early pathogenesis of human NSCLC.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, NO. 1, Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, 610041, Chengdu, Sichuan, P. R. China. wangyu_4932@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, NO. 1, Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, 610041, Chengdu, Sichuan, P. R. China. younger1030@163.com.
authors.forename: Weihan
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, 610041, Chengdu, Sichuan, P. R. China. puqiang11@gmail.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Pu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, NO. 1, Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, 610041, Chengdu, Sichuan, P. R. China. scu_yanyang@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, NO. 1, Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, 610041, Chengdu, Sichuan, P. R. China. shiny9191@163.com.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, NO. 1, Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, 610041, Chengdu, Sichuan, P. R. China. qingpingle2008@163.com.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, NO. 1, Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, 610041, Chengdu, Sichuan, P. R. China. rjham@126.com.
authors.forename: Jiang
authors.initials: J
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, NO. 1, Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, 610041, Chengdu, Sichuan, P. R. China. caozhixing007@163.com.
authors.forename: Zhixing
authors.initials: Z
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, NO. 1, Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, 610041, Chengdu, Sichuan, P. R. China. guoxingzhong@gmail.com.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, NO. 1, Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, 610041, Chengdu, Sichuan, P. R. China. 42539791@qq.com.
authors.forename: Xuechao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, 610041, Chengdu, Sichuan, P. R. China. lunxu_liu@aliyun.com.
authors.forename: Lunxu
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, NO. 1, Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, 610041, Chengdu, Sichuan, P. R. China. zhuwen@scu.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhu
mesh_terms: D000368:Aged; D063646:Carcinogenesis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C493557:SLC34A2 protein, human; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D019869:Phosphatidylinositol 3-Kinases