English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Sphere formation in conditioned serum‐free culture medium supplemented with epidermal growth factor and basic fibroblast growth factor (tumorospheres) is considered useful for the enrichment of cancer stem‐like cells, also known as tumor‐initiating cells. We used a gene expression microarray to investigate the gene expression profile of melanoma cancer stem‐like cells ( MCSLC s). The results showed that  MCSLC s highly expressed the following Notch signaling pathway molecules: Notch3 ( NM _008716), Notch4 ( NM _010929), Dtx4 ( NM _172442), and  JAG 2 ( NM _010588). Immunofluorescence staining showed tumorosphere cells highly expressed Notch4. Notch4 high  B16F10 cells were isolated by  FACS , and Western blotting showed that high Notch4 expression is related to the expression of epithelial–mesenchymal transition ( EMT )‐associated proteins. Reduced invasive and migratory properties concomitant with the downregulation of the  EMT  markers Twist1, vimentin, and  VE ‐cadherin and the overexpression of E‐cadherin was observed in human melanoma A375 and  MUM ‐2B cells. In these cells, Notch4 was also downregulated, both by  Notch4  gene knockdown and by application of the γ‐secretase inhibitor,  DAPT . Mechanistically, the re‐overexpression of Twist1 by the transfection of cells with a Twist1 expression plasmid led to an increase in  VE ‐cadherin expression and a decrease in E‐cadherin expression. Immunohistochemical analysis of 120 human melanoma tissues revealed a significant correlation between the high expression of Notch4 and the metastasis of melanoma. Taken together, our findings indicate that Notch4+  MCSLC s trigger  EMT  and promote the metastasis of melanoma cells.

Notch4+ cancer stem‐like cells promote the metastatic and invasive ability of melanoma