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2015 ; 34
(ä): 110
Nephropedia Template TP
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Basigin-mediated redistribution of CD98 promotes cell spreading and
tumorigenicity in hepatocellular carcinoma
#MMPMID26437640
Wu B
; Wang Y
; Yang XM
; Xu BQ
; Feng F
; Wang B
; Liang Q
; Li Y
; Zhou Y
; Jiang JL
; Chen ZN
J Exp Clin Cancer Res
2015[Oct]; 34
(ä): 110
PMID26437640
show ga
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. CONCLUSION: Basigin, as a redistribution
chaperone of CD98, plays a critical role in promoting cell spreading and the
progression of hepatocellular carcinoma.