Novel glycoprotein SBSPON suppressed bladder cancer through the AKT signal pathway by inhibiting HSPA5 membrane translocation
Bladder cancer poses severe threats to human health due to its aggressive nature and resistance to drug treatment; however, the underlying mechanisms have not been fully investigated. In the present study, we identify SBSPON (Somatomedin B and Thrombospondin Type 1 Domain Containing) as a novel tumor suppressor. The expression of SBSPON was downregulated in bladder cancer and correlated with poor overall survival. SBSPON suppressed the proliferation and migration ability of bladder cancer cells <i>in vitro</i>, and inhibited tumor growth of bladder cancer cells <i>in vivo</i>. Genetic ablation of <i>Sbspon</i> in mice significantly accelerated the progression of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) induced bladder cancer. Mechanistically, SBSPON is a novel HSPA5 binding glycoprotein. SBSPON functioned through binding to HSPA5 and inhibiting its membrane translocation, resulting in an inactivated AKT signaling pathway. More importantly, SBSPON inhibited the cisplatin resistance of bladder cancer cells by reducing the inhibitory effect of HSPA5 on apoptosis. In summary, the novel glycoprotein SBSPON functions as a tumor suppressor and inhibits resistance to cisplatin in bladder cancer. This may provide novel therapeutic strategies for bladder cancer treatment.
Authors
- Shasha Min
- Xina Xie (ORCID: https://orcid.org/0000-0002-0193-090X)
- Linbo Gao (ORCID: https://orcid.org/0000-0002-7572-8990)
- Xianxin Li (ORCID: https://orcid.org/0000-0002-5690-0150)
- Zesong Li (ORCID: https://orcid.org/0000-0003-0975-4434)
- Wei Yang (ORCID: https://orcid.org/0000-0001-7993-8170)
- Beibei Ni (ORCID: https://orcid.org/0009-0000-3502-7957)
- John R. Speakman (ORCID: https://orcid.org/0000-0002-2457-1823)
- Lan Zhao (ORCID: https://orcid.org/0000-0003-2681-7695)
- Zhiming Cai (ORCID: https://orcid.org/0009-0006-4307-8272)
- Li Shi (ORCID: https://orcid.org/0000-0001-9508-7863)
- Yizhen Wang (ORCID: https://orcid.org/0000-0002-3908-7102)
- Liya Luo
- Yuqi Zhu (ORCID: https://orcid.org/0000-0002-2553-8021)
- Junwen Zhang (ORCID: https://orcid.org/0000-0001-8041-1608)
Institutions
- North Sichuan Medical University (CN)
- Sun Yat-sen University (CN)
- University of Aberdeen (GB)
- Chinese Academy of Sciences (CN)
- Agriculture and Forestry University (NP)
- Shantou University (CN)
- North West Agriculture and Forestry University (CN)
- Longgang Central Hospital (CN)
- Yue Bei People's Hospital (CN)
- Institute of Genetics and Developmental Biology (CN)
- Shenzhen Institutes of Advanced Technology (CN)
- Third Affiliated Hospital of Sun Yat-sen University (CN)
- Shenzhen Second People's Hospital (CN)
- University of Agriculture Faisalabad (PK)
- China Medical University (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- International Journal of Biological Sciences
- Published
- 2025-07-11
- DOI
- https://doi.org/10.7150/ijbs.109973
- Citations
- 1
- Primary Topic
- Hormonal Regulation and Hypertension
- Type
- article
- Field-Weighted Citation Impact
- 1.29
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Guangdong Province