TSPAN15 interacts with BTRC to promote oesophageal squamous cell carcinoma metastasis via activating NF-κB signaling.

Beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) is crucial for the degradation of IκBα. Our previous transcriptome sequencing analysis revealed that tetraspanin 15 was significantly upregulated in clinical oesophageal squamous cell carcinoma (OSCC) tissues. Here, we show that high expression in OSCC tissues is significantly associated with lymph node and distant metastasis, advanced clinical stage, and poor prognosis. Elevated Tduanyu1842N15 expression is, in part, caused by the reduction of miR-339-5p. Functional studies demonstrate that Tduanyu1842N15 promotes metastatic capabilities of OSCC cells. We further show that Tduanyu1842N15 specifically interacts with BTRC to promote the ubiquitination and proteasomal degradation of p-IκBα, and thereby triggers NF-κB nuclear translocation and subsequent activation of transcription of several metastasis-related genes, including ICAM1, VCAM1, uPA, MMP9, TNFα, and CCL2. Collectively, our findings indicate that Tduanyu1842N15 may serve as a new biomarker and/or provide a novel therapeutic target to OSCC patients.

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