TRAF6 regulates EGF-induced cell transformation and cSCC malignant phenotype through CD147/EGFR

Oncogenesis
Xu ZhangCong Peng

Abstract

TRAF6, a well-known adapter molecule, plays pivotal role in TLR/IL-1R associated signaling pathway. Although TRAF6 has been shown to have oncogenic activity in various malignant tumors, the details remain unclear. In this study, we demonstrated that TRAF6 facilitates Ras (G12V) and EGF-induced cellular transformation through EGFR. Silencing of TRAF6 expression significantly downregulated AP-1 activity, as well as MMP-2,9 expression after EGF stimulation. Furthermore, we found that TRAF6 plays an essential role in cutaneous squamous cell carcinoma (cSCC) malignant phenotypes, affecting cell growth and migration. CD147/Basigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, is over-expressed in tumors and induces tumorigenesis. Our results showed that CD147 formed complex with EGFR and TRAF6. Knockdown of TRAF6 disrupted the CD147-EGFR complex, thereby inducing EGFR endocytosis. Therefore, TRAF6 might be a novel molecular target for cSCC prevention or therapy.

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Citations

Oct 9, 2018·Frontiers in Immunology·Sining ZhuPing Xie
Dec 24, 2019·Frontiers in Genetics·Joanna PyczekHeidi Hahn
May 22, 2020·Journal of Cellular and Molecular Medicine·Yi-Lin HuWan-Jiang Xue
Sep 10, 2020·Cancer Cell International·Jiaoduan LiCong Peng
Feb 16, 2021·Otolaryngologic Clinics of North America·Alok R KhandelwalCherie Ann Nathan

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Methods Mentioned

BETA
surgical resection
PCR
xenograft
Antibody Array
protein array
immunoprecipitation
confocal microscopy
ubiquitination
nucleotide exchange
transfection

Software Mentioned

ImageJ
PathScan

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