TSPAN15 interacts with BTRC to promote oesophageal squamous cell carcinoma metastasis via activating NF-κB signaling
2018
Beta-
transducinrepeat containing E3 ubiquitin protein ligase (
BTRC) is crucial for the degradation of
IκBα. Our previous transcriptome sequencing analysis revealed that
tetraspanin15 (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-339-5p. Functional studies demonstrate that TSPAN15 promotes metastatic capabilities of OSCC cells. We further show that TSPAN15 specifically interacts with
BTRCto 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 TSPAN15 may serve as a new biomarker and/or provide a novel therapeutic target to OSCC patients.
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