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Journal of Experimental and Clinical Cancer Research

, 34:110

First Online: 06 October 2015Received: 27 August 2015Accepted: 29 September 2015DOI: 10.1186-s13046-015-0226-6

Cite this article as: Wu, B., Wang, Y., Yang, XM. et al. J Exp Clin Cancer Res 2015 34: 110. doi:10.1186-s13046-015-0226-6

Abstract

BackgroundDysregulated 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.

MethodsThe 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.

ResultsBasigin 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.

ConclusionBasigin, as a redistribution chaperone of CD98, plays a critical role in promoting cell spreading and the progression of hepatocellular carcinoma.

KeywordsHepatocellular carcinoma Basigin CD98 Distribution Endosomes Progression AbbreviationsHCCHuman hepatocellular carcinoma

RTKsReceptor tyrosine kinases

CMEClathrin-mediated endocytosis

CIEClathrin-independent endocytosis

EMMPRINExtracellular matrix metalloproteinase inducer

EREndoplasmic reticulum

EAAEssential amino acids

MIDASMetal ion-dependent adhesion site

EEA1Early endosome antigen-1

FRETFluorescence resonance energy transfer

Bo Wu, Yi Wang and Xiang-Min Yang contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s13046-015-0226-6 contains supplementary material, which is available to authorized users.

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Autor: Bo Wu - Yi Wang - Xiang-Min Yang - Bao-Qing Xu - Fei Feng - Bin Wang - Qiang Liang - Yu Li - Yang Zhou - Jian-Li Jiang -

Fuente: https://link.springer.com/



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