title: Basigin-mediated redistribution of CD98 promotes cell spreading and tumorigenicity in hepatocellular carcinoma.
abstract: BACKGROUND
  Dysregulated endocytosis of membrane proteins contributes significantly to several hallmarks of cancer. Basigin can enhance cancer progression, but its precise mechanism remains unclear. CD98 promotes cell spreading and tumorigenicity by triggering integrin clustering and enhancing cell adhesion to the extracellular matrix. The endocytosis and recyle of basigin and CD98 might play critical roles in cancer.
  
  
  METHODS
  The role of CD98 was confirmed in liver cancer cells by cell spreading in vitro and tumorigenicity by nude mice xenograft tumor assay in vivo; membrane expression of basigin and CD98 in SMMC-7721 was measured by FCAS; pull down and SPR analysis were uses to reveal the direct association between basigin and CD98; DsRed1 tagged CD98 was blocked in the cytoplasm in K7721 (whose basigin was knockn out) and had a well colocalization with ER and Rab5a positive recycling endosomes under co-focal; finally, by FRET imaging and FCAS we observed the internalization of basigin and CD98 was flotillin-1-regulated, and their recycle at early steps was Arf6-mediated.
  
  
  RESULTS
  Basigin and CD98 were highly expressed and co-localized on the human hepatocellular carcinoma (HCC) cell membrane; basigin can directly bind to CD98, mediating CD98 redistribution on the HCC cell membrane and activating the downstream integrin signaling pathway. Internalization of basigin and CD98 was flotillin-1 regulated the and their recycling was mediated by Arf6. This recycling process for basigin and CD98 promotes cell spreading and tumor growth in liver cancer xenografts.
  
  
  CONCLUSIONS
  Basigin, as a redistribution chaperone of CD98, plays a critical role in promoting cell spreading and the progression of hepatocellular carcinoma.
authors.affiliation: Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, P. R. China. soldier2158wubo@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.affiliation: Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, P. R. China. www.yiwang888@126.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, P. R. China. yxiangmind@163.com.
authors.forename: Xiang-Min
authors.initials: XM
authors.lastname: Yang
authors.affiliation: Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, P. R. China. 826020394@qq.com.
authors.forename: Bao-Qing
authors.initials: BQ
authors.lastname: Xu
authors.affiliation: Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, P. R. China. fengfei122@126.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Feng
authors.affiliation: Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, P. R. China. kingpoem@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, P. R. China. ringnoo39@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, P. R. China. liyufmmu@yahoo.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, P. R. China. 1137659695@qq.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, P. R. China. jiangjl@fmmu.edu.cn.
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Jiang
authors.affiliation: Cell Engineering Research Centre & Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, P. R. China. zhinanchen@fmmu.edu.cn.
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Chen
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000818:Animals; D051926:Basigin / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004705:Endocytosis / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D027261:Fusion Regulatory Protein-1 / Q000235:genetics*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D020349:Surface Plasmon Resonance; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000089982:ADP-Ribosylation Factor 6; D027261:Fusion Regulatory Protein-1; D016023:Integrins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C106354:flotillins; D051926:Basigin; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; C000715727:Arf6 protein, mouse