Novel Impact of EWI-2, CD9, and CD81 on TGF-β Signaling in Melanoma

Overview

Journal Mol Cell Oncol

Specialty Oncology

Date 2016 Mar 19

PMID 26989766

Citations 7

Authors

Hong-Xing Wang

Martin E Hemler

Affiliations

Soon will be listed here.

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.

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References

Akhurst R, Hata A . Targeting the TGFβ signalling pathway in disease. Nat Rev Drug Discov. 2012; 11(10):790-811. PMC: 3520610. DOI: 10.1038/nrd3810. View

Padua D, Massague J . Roles of TGFbeta in metastasis. Cell Res. 2008; 19(1):89-102. DOI: 10.1038/cr.2008.316. View

Wang H, Sharma C, Knoblich K, Granter S, Hemler M . EWI-2 negatively regulates TGF-β signaling leading to altered melanoma growth and metastasis. Cell Res. 2015; 25(3):370-85. PMC: 4349253. DOI: 10.1038/cr.2015.17. View

Perrot C, Javelaud D, Mauviel A . Insights into the Transforming Growth Factor-β Signaling Pathway in Cutaneous Melanoma. Ann Dermatol. 2013; 25(2):135-44. PMC: 3662904. DOI: 10.5021/ad.2013.25.2.135. View

Scherf U, Ross D, Waltham M, Smith L, Lee J, Tanabe L . A gene expression database for the molecular pharmacology of cancer. Nat Genet. 2000; 24(3):236-44. DOI: 10.1038/73439. View