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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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EWI-2 regulates melanoma growth and lung metastasis in a TGF-M-NM-21-dependent manner

ABSTRACT: EWI-2 (IgSF8) plays a novel, bifunctional role in melanoma cells. EWI-2 inhibits migration, metastasis, EMT-like changes, and CD271-dependent invasion in multiple melanoma cell lines. On the other hand, EWI-2 supports melanoma cell proliferation, survival, and xenograft growth. Consistent with these results, EWI-2 levels were elevated in human malignant melanoma, but not in metastatic melanoma samples. Altered melanoma cell functions, caused by EWI-2 ablation, are almost entirely dependent on enhanced TRF-M-NM-21 signaling, and also require contributions from tetraspanin proteins CD9 and CD81. In melanoma cells lacking EWI-2, tetraspanins CD9 and CD81 enhance TRF-M-NM-21 signaling by facilitating TM-NM-2R-2M-bM-^HM-^RTM-NM-2R-1 receptor complex formation. When EWI-2 is present, CD9 and CD81 are diverted into EWI-2 complexes, and thus TRF-M-NM-21 signaling is inhibited. 4 samples = 2 Control + 2 EWI-2 KD.

ORGANISM(S): Homo sapiens

SUBMITTER: Konstantin Knoblich

PROVIDER: E-GEOD-47978 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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EWI-2 regulates melanoma growth and lung metastasis in a TGF-β1-dependent manner

Project description:EWI-2 (IgSF8) plays a novel, bifunctional role in melanoma cells. EWI-2 inhibits migration, metastasis, EMT-like changes, and CD271-dependent invasion in multiple melanoma cell lines. On the other hand, EWI-2 supports melanoma cell proliferation, survival, and xenograft growth. Consistent with these results, EWI-2 levels were elevated in human malignant melanoma, but not in metastatic melanoma samples. Altered melanoma cell functions, caused by EWI-2 ablation, are almost entirely dependent on enhanced TRF-β1 signaling, and also require contributions from tetraspanin proteins CD9 and CD81. In melanoma cells lacking EWI-2, tetraspanins CD9 and CD81 enhance TRF-β1 signaling by facilitating TβR-2−TβR-1 receptor complex formation. When EWI-2 is present, CD9 and CD81 are diverted into EWI-2 complexes, and thus TRF-β1 signaling is inhibited.

2013-06-15 | GSE47978 | GEO

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