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


ABSTRACT: Beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) is crucial for the degradation of I?B?. 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-339-5p. 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?B?, and thereby triggers NF-?B nuclear translocation and subsequent activation of transcription of several metastasis-related genes, including ICAM1, VCAM1, uPA, MMP9, TNF?, and CCL2. Collectively, our findings indicate that TSPAN15 may serve as a new biomarker and/or provide a novel therapeutic target to OSCC patients.

SUBMITTER: Zhang B 

PROVIDER: S-EPMC5897412 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Zhang Baozhu B   Zhang Zhao Z   Li Lei L   Qin Yan-Ru YR   Liu Haibo H   Jiang Chen C   Zeng Ting-Ting TT   Li Meng-Qing MQ   Xie Dan D   Li Yan Y   Guan Xin-Yuan XY   Guan Xin-Yuan XY   Zhu Ying-Hui YH  

Nature communications 20180412 1


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 (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  ...[more]

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