Mechanistic insights into PROS1 inhibition of bladder cancer progression and angiogenesis via the AKT/GSK3β/β-catenin pathway
Abstract Bladder cancer (BLCA) is one of the ten most common cancers worldwide. However, the deregulation of PROS1 and its specific function in BLCA is not well understood. By combining proteomic and transcriptomic datasets, we discovered PROS1 expression was significantly reduced in BLCA tissues an...
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-89217-4 |
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| author | Xin-peng Fan Ji-rong Wang Si-yu Chen Xiao-ran Li Jin-long Cao Hua-bin Wang Li-yun Ding Tuan-jie Che Li Yang |
| author_facet | Xin-peng Fan Ji-rong Wang Si-yu Chen Xiao-ran Li Jin-long Cao Hua-bin Wang Li-yun Ding Tuan-jie Che Li Yang |
| author_sort | Xin-peng Fan |
| collection | DOAJ |
| description | Abstract Bladder cancer (BLCA) is one of the ten most common cancers worldwide. However, the deregulation of PROS1 and its specific function in BLCA is not well understood. By combining proteomic and transcriptomic datasets, we discovered PROS1 expression was significantly reduced in BLCA tissues and revealed the clinical relevance of PROS1 with BLCA. Analysis of multiple BLCA datasets consistently showed the group with reduced PROS1 expression was linked to cancer-promoting pathways, more aggressive characteristics, and a greater chance of responding positively to immunotherapy. Next, various functional experiments were performed and the results revealed PROS1 overexpression inhibited the proliferation, cell cycle progression, migration, invasion, and angiogenesis of BLCA. In recovery trials, the AKT activator SC79 offered additional proof that PROS1 may influence BLCA cells via the AKT/GSK3β/β-catenin pathway. In conclusion, as an angiogenesis-related gene, PROS1 may play an inhibitory role in the biological functions of bladder cancer. |
| format | Article |
| id | doaj-art-1727d8eddfb5433c9bfb2604cba3f89e |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-1727d8eddfb5433c9bfb2604cba3f89e2025-02-09T12:32:03ZengNature PortfolioScientific Reports2045-23222025-02-0115112310.1038/s41598-025-89217-4Mechanistic insights into PROS1 inhibition of bladder cancer progression and angiogenesis via the AKT/GSK3β/β-catenin pathwayXin-peng Fan0Ji-rong Wang1Si-yu Chen2Xiao-ran Li3Jin-long Cao4Hua-bin Wang5Li-yun Ding6Tuan-jie Che7Li Yang8Department of Urology, The Second Hospital of Lanzhou UniversityDepartment of Urology, The Second Hospital of Lanzhou UniversityDepartment of Urology, The Second Hospital of Lanzhou UniversityDepartment of Urology, The Second Hospital of Lanzhou UniversityDepartment of Urology, The Second Hospital of Lanzhou UniversityDepartment of Urology, The Second Hospital of Lanzhou UniversitySchool of Physical Science and Technology, Lanzhou UniversityBaiyuan Company for Gene TechnologyDepartment of Urology, The Second Hospital of Lanzhou UniversityAbstract Bladder cancer (BLCA) is one of the ten most common cancers worldwide. However, the deregulation of PROS1 and its specific function in BLCA is not well understood. By combining proteomic and transcriptomic datasets, we discovered PROS1 expression was significantly reduced in BLCA tissues and revealed the clinical relevance of PROS1 with BLCA. Analysis of multiple BLCA datasets consistently showed the group with reduced PROS1 expression was linked to cancer-promoting pathways, more aggressive characteristics, and a greater chance of responding positively to immunotherapy. Next, various functional experiments were performed and the results revealed PROS1 overexpression inhibited the proliferation, cell cycle progression, migration, invasion, and angiogenesis of BLCA. In recovery trials, the AKT activator SC79 offered additional proof that PROS1 may influence BLCA cells via the AKT/GSK3β/β-catenin pathway. In conclusion, as an angiogenesis-related gene, PROS1 may play an inhibitory role in the biological functions of bladder cancer.https://doi.org/10.1038/s41598-025-89217-4Bladder cancerPROS1AngiogenesisBioinformaticsVitro and vivo functional experiment |
| spellingShingle | Xin-peng Fan Ji-rong Wang Si-yu Chen Xiao-ran Li Jin-long Cao Hua-bin Wang Li-yun Ding Tuan-jie Che Li Yang Mechanistic insights into PROS1 inhibition of bladder cancer progression and angiogenesis via the AKT/GSK3β/β-catenin pathway Scientific Reports Bladder cancer PROS1 Angiogenesis Bioinformatics Vitro and vivo functional experiment |
| title | Mechanistic insights into PROS1 inhibition of bladder cancer progression and angiogenesis via the AKT/GSK3β/β-catenin pathway |
| title_full | Mechanistic insights into PROS1 inhibition of bladder cancer progression and angiogenesis via the AKT/GSK3β/β-catenin pathway |
| title_fullStr | Mechanistic insights into PROS1 inhibition of bladder cancer progression and angiogenesis via the AKT/GSK3β/β-catenin pathway |
| title_full_unstemmed | Mechanistic insights into PROS1 inhibition of bladder cancer progression and angiogenesis via the AKT/GSK3β/β-catenin pathway |
| title_short | Mechanistic insights into PROS1 inhibition of bladder cancer progression and angiogenesis via the AKT/GSK3β/β-catenin pathway |
| title_sort | mechanistic insights into pros1 inhibition of bladder cancer progression and angiogenesis via the akt gsk3β β catenin pathway |
| topic | Bladder cancer PROS1 Angiogenesis Bioinformatics Vitro and vivo functional experiment |
| url | https://doi.org/10.1038/s41598-025-89217-4 |
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