SBSN drives bladder cancer metastasis via EGFR/SRC/STAT3 signalling
SBSN drives bladder cancer metastasis via EGFR/SRC/STAT3 signalling
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DOI：
10.1038/s41416-022-01794-7
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发表时间：
2022-04
影响因子：
8.8
通讯作者：
Zhongqiu Zhou;Zhuojun Zhang;Han Chen;Wenhao Bao;Xiangqin Kuang;Ping Zhou;Zhiqing Gao;Difeng Li-Di
中科院分区：
文献类型：
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作者：
Zhongqiu Zhou;Zhuojun Zhang;Han Chen;Wenhao Bao;Xiangqin Kuang;Ping Zhou;Zhiqing Gao;Difeng Li-Di
背景转移性膀胱癌患者预后非常差，迫切需要具有预测性的生物标志物进行早期临床检测和干预。在本研究中，我们探讨了Suprabasin （SBSN）在膀胱癌转移中的作用及其机制。方法采用sa组织阵列免疫组化检测SBSN的表达。采用荷瘤小鼠模型进行体内转移评估。采用Transwell法和创面愈合法体外评估迁移和侵袭。通过western blotting、免疫荧光、荧光素酶报告基因测定和ELISA进行全面的分子筛选。结果ssbsn在膀胱癌中明显过表达，预后较差。SBSN在体内和体外均能促进膀胱癌细胞的侵袭和转移。分泌的SBSN在膀胱癌转移中表现出相同的生物学功能和调控，分泌的SBSN与EGFR的相互作用可能在激活SBSN增强EGFR和SRC激酶磷酸化、STAT3磷酸化和核定位的信号通路中发挥重要作用。结论SBSN及其分泌的SBSN通过激活EGFR/SRC/STAT3通路促进膀胱癌转移，是膀胱癌潜在的诊断和治疗靶点。
BackgroundPatients with metastatic bladder cancer have very poor prognosis and predictive biomarkers are urgently needed for early clinical detection and intervention. In this study, we evaluate the effect and mechanism of Suprabasin (SBSN) on bladder cancer metastasis.MethodsA tissue array was used to detect SBSN expression by immunohistochemistry. A tumour-bearing mouse model was used for metastasis evaluation in vivo. Transwell and wound-healing assays were used for in vitro evaluation of migration and invasion. Comprehensive molecular screening was achieved by western blotting, immunofluorescence, luciferase reporter assay, and ELISA.ResultsSBSN was found markedly overexpressed in bladder cancer, and indicated poor prognosis of patients. SBSN promoted invasion and metastasis of bladder cancer cells both in vivo and in vitro. The secreted SBSN exhibited identical biological function and regulation in bladder cancer metastasis, and the interaction of secreted SBSN and EGFR could play an essential role in activating the signalling in which SBSN enhanced the phosphorylation of EGFR and SRC kinase, followed with phosphorylation and nuclear location of STAT3.ConclusionsOur findings highlight that SBSN, and secreted SBSN, promote bladder cancer metastasis through activation of EGFR/SRC/STAT3 pathway and identify SBSN as a potential diagnostic and therapeutic target for bladder cancer.