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Published on: October 27, 2020
Novel impact of EWI-2, CD9, and CD81 on TGF-β signaling in melanoma
Hong-Xing Wang1, Martin E Hemler1
1Department of Cancer Immunology and AIDS; Dana-Farber Cancer Institute and Department of Pathology; Harvard Medical School; Boston, MA USA.
Abstract:
Cell surface transmembrane protein IGFS8 (herein called EWI-2) negatively regulates melanoma TGF-β signaling and is well positioned to control the transition in TGF-β signaling from cytostatic (in early melanoma stages) to pro-invasion/metastasis (in later stages). EWI-2 functions by sequestering the tetraspanin proteins CD9 and CD81, thereby making them unavailable to support the association of TGFβ receptor 1 with TGFβ receptor 2.
Insights
EWI-2 protein regulates melanoma cell signaling by controlling transforming growth factor-beta (TGF-β) activity. This protein impacts melanoma progression from early to later stages by influencing TGF-β
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Melanoma progression involves a shift in transforming growth factor-beta (TGF-β) signaling from cytostatic to pro-metastatic.
- Cell surface proteins play critical roles in regulating cell signaling pathways.
Purpose of the Study:
- To investigate the role of the cell surface transmembrane protein EWI-2 in regulating melanoma TGF-β signaling.
- To understand how EWI-2 influences the transition of melanoma from early to advanced stages.
Main Methods:
- Investigated the function of EWI-2 in melanoma cell lines.
- Analyzed the interaction of EWI-2 with tetraspanin proteins CD9 and CD81.
- Assessed the impact of EWI-2 on TGF-β receptor complex formation.
Main Results:
- EWI-2 negatively regulates melanoma TGF-β signaling.
- EWI-2 sequesters CD9 and CD81, preventing their support of TGFβ receptor 1 and TGFβ receptor 2 association.
- EWI-2 is positioned to control the switch in TGF-β signaling during melanoma progression.
Conclusions:
- EWI-2 acts as a key regulator of melanoma TGF-β signaling.
- Targeting EWI-2 may offer therapeutic strategies for controlling melanoma invasion and metastasis.
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