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Cellular and Molecular Biology

SBSN drives bladder cancer metastasis via EGFR/SRC/STAT3 signalling

British Journal of Cancer volume 127, pages 211–222 (2022) Cite this article

Subjects

Abstract

Background

Patients 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.

Methods

A 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.

Results

SBSN 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.

Conclusions

Our 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.

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Fig. 1: SBSN is upregulated and associated with the progression of bladder cancer.
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Fig. 2: SBSN enhanced bladder cancer aggressiveness.
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Fig. 3: Secreted SBSN enhanced bladder cancer aggressiveness.
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Fig. 4: SBSN activated EGFR/SRC/STAT3 signalling pathway.
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Fig. 5: Secreted SBSN activated EGFR/SRC/STAT3 signalling pathway.
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Fig. 6: SBSN activated EGFR/STAT3 signalling pathway in vivo.
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Data availability

The data that support the findings of this work are available from the corresponding author upon request.

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Funding

The Natural Science Foundation of Guangdong Province (2021A1515012477), the Natural Science Foundation of China (81972619, 81672874), the Basic and Applied Research Projects of Guangzhou Science and Technology Bureau (202002030067), the Natural Science Foundation research team of Guangdong Province (2018B030312001), the open research funds from the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital (202011–202), the Innovative Academic Team of Guangzhou Education System (1201610014), the Key Discipline of Guangzhou Education Bureau (Basic Medicine) (201851839), the Guangzhou key medical discipline construction project fun.

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Author notes

  1. These authors contributed equally: Zhongqiu Zhou, Zhuojun Zhang, Han Chen.

Authors and Affiliations

  1. Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 510095, Guangzhou, China

    Zhongqiu Zhou, Zhuojun Zhang, Han Chen, Wenhao Bao, Xiangqin Kuang, Ping Zhou, Zhiqing Gao, Difeng Li, Xiaoyi Xie, Chunxiao Yang, Jianan Yang & Lili Jiang

  2. Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Science, Guangzhou Medical University, 511436, Guangzhou, China

    Zhongqiu Zhou, Zhuojun Zhang, Han Chen, Wenhao Bao, Xiangqin Kuang, Ping Zhou, Zhiqing Gao, Difeng Li, Xiaoyi Xie, Chunxiao Yang & Lili Jiang

  3. Meishan Women and Children’s Hospital, Alliance Hospital of West China Second University Hospital, Sichuan University, 620000, Meishan, China

    Zhongqiu Zhou

  4. Medical Research Center, Southern University of Science and Technology Hospital, 518055, Shenzhen, China

    Xuhong Chen

  5. Department of Oncology, Huanggang Central Hospital of Yangtze University, 438000, Huanggang, China

    Jinyuan Pan

  6. The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, 511518, Guangzhou, China

    Ruiming Tang, Zhengfu Feng & Lihuan Zhou

  7. Department of Pathogen Biology and Immunology, School of Basic Courses, Guangdong Pharmaceutical University, 510006, Guangzhou, China

    Lan Wang

  8. Department of Urologic Oncosurgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 510095, Guangzhou, China

    Jianan Yang

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  1. Zhongqiu Zhou
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Contributions

LJ and JY developed the original idea, designed the study, analysed data, and wrote the manuscript. ZZ, ZZ and HC contributed to the development of the protocol and performed most of the experiments and data analysis. WB, XK, PZ, ZG, XX, CY and JP contributed to the in vitro biological experiments and data analysis., ZZ, ZZ, HC, DL and XC performed the in vivo experiments and data analysis. RT, ZF, and LZ contributed to clinical data collection and statistical analysis. LW provided the bioinformatics analysis.

Corresponding authors

Correspondence to Jianan Yang or Lili Jiang.

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Zhou, Z., Zhang, Z., Chen, H. et al. SBSN drives bladder cancer metastasis via EGFR/SRC/STAT3 signalling. Br J Cancer 127, 211–222 (2022). https://doi.org/10.1038/s41416-022-01794-7

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