期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-018-03716-9
关键词
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资金
- Hong Kong Research Grant Council (RGC) [C7038-14G, C7027-14G, HKU/7668/11M, 767313, CUHK/766613]
- NSFC/RGC Joint Research Scheme, Hong Kong [CUHK/766613, N_HKU712/12]
- NSFC/RGC Joint Research Scheme [N_HKU712/12]
- Hong Kong Health and Medical Research Fund [02133366]
- National Basic Research Program of China [2012CB967001]
- China National Key Sci-Tech Special Project of Infectious Diseases [2013ZX10002-011-005]
- Young Talent Teachers Plan of Sun Yat-sen University [15ykpy33]
Beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) is crucial for the degradation of I kappa B alpha. Our previous transcriptome sequencing analysis revealed that tetraspanin 15 (TSPAN15) was significantly upregulated in clinical oesophageal squamous cell carcinoma (OSCC) tissues. Here, we show that high TSPAN15 expression in OSCC tissues is significantly associated with lymph node and distant metastasis, advanced clinical stage, and poor prognosis. Elevated TSPAN15 expression is, in part, caused by the reduction of miR-3395p. Functional studies demonstrate that TSPAN15 promotes metastatic capabilities of OSCC cells. We further show that TSPAN15 specifically interacts with BTRC to promote the ubiquitination and proteasomal degradation of p-I kappa B alpha, and thereby triggers NF-kappa B nuclear translocation and subsequent activation of transcription of several metastasis-related genes, including ICAM1, VCAM1, uPA, MMP9, TNF alpha, and CCL2. Collectively, our findings indicate that TSPAN15 may serve as a new biomarker and/or provide a novel therapeutic target to OSCC patients.
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