PKIB facilitates bladder cancer proliferation and metastasis through mediation of HSP27 phosphorylation by PKA
Abstract Cyclic AMP-dependent protein kinase A (PKA) is recognized for its pivotal involvement in various cancer types, with Protein Kinase Inhibitor Beta (PKIB) serving as an endogenous inhibitor that curtails PKA activity. Despite the documented escalation of PKIB expression in several malignancie...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-07-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07814-7 |
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| author | Xiaolong Liu Xiaoyu Yin Feng Yuan Shiqing Li Fei Xiao Feng Zhou Xudong Pan Yatfaat Ho Shuo Dong Duan Xu Yunqing Ma Zhengding Cao Zhe Lei Yi Sun |
| author_facet | Xiaolong Liu Xiaoyu Yin Feng Yuan Shiqing Li Fei Xiao Feng Zhou Xudong Pan Yatfaat Ho Shuo Dong Duan Xu Yunqing Ma Zhengding Cao Zhe Lei Yi Sun |
| author_sort | Xiaolong Liu |
| collection | DOAJ |
| description | Abstract Cyclic AMP-dependent protein kinase A (PKA) is recognized for its pivotal involvement in various cancer types, with Protein Kinase Inhibitor Beta (PKIB) serving as an endogenous inhibitor that curtails PKA activity. Despite the documented escalation of PKIB expression in several malignancies, a comprehensive understanding of its precise mechanistic implications in human cancers remains elusive. This investigation is centered on bladder cancer (BLCA), unveiling an augmented expression of PKIB concomitant with heightened BLCA cell proliferation, migration, and invasion in vitro and augmented tumorigenic potential in an in vivo model. Mechanistically, PKIB disrupts PKA kinase activity, thereby resulting in diminished phosphorylation of the substrate target protein HSP27 at serine 15, 78, and 82. Additionally, the transcription factor MYCN exhibits an affinity for the PKIB promoter, leading to its enhanced expression in the context of BLCA. These findings reveal the oncogenic proclivity of PKIB and introduce a novel signalling pathway in BLCA, providing valuable insights into potential therapeutic targets for precise intervention. |
| format | Article |
| id | doaj-art-cebbdf461fe64bdfb07ebd57e6a0e7fe |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-cebbdf461fe64bdfb07ebd57e6a0e7fe2025-08-20T03:42:00ZengNature Publishing GroupCell Death and Disease2041-48892025-07-0116112010.1038/s41419-025-07814-7PKIB facilitates bladder cancer proliferation and metastasis through mediation of HSP27 phosphorylation by PKAXiaolong Liu0Xiaoyu Yin1Feng Yuan2Shiqing Li3Fei Xiao4Feng Zhou5Xudong Pan6Yatfaat Ho7Shuo Dong8Duan Xu9Yunqing Ma10Zhengding Cao11Zhe Lei12Yi Sun13Department of Urology, The Second Affiliated Hospital of Soochow UniversityDepartment of Genetics, School of Basic Medical Sciences, Suzhou Medical College of Soochow UniversityDepartment of Urology, The Second Affiliated Hospital of Soochow UniversityDepartment of Urology, The First Affiliated Hospital of Soochow UniversityDepartment of Bioinformatics and Computational Biology, School of Life Sciences, Suzhou Medical College of Soochow UniversityDepartment of Urology, The First Affiliated Hospital of Soochow UniversityDepartment of General Medicine, The First Affiliated Hospital of Soochow UniversityDepartment of Urology, Suzhou BenQ Medical CenterDepartment of Genetics, School of Basic Medical Sciences, Suzhou Medical College of Soochow UniversityDepartment of Genetics, School of Basic Medical Sciences, Suzhou Medical College of Soochow UniversityDepartment of Bioinformatics and Computational Biology, School of Life Sciences, Suzhou Medical College of Soochow UniversityInstitute of Epidemiology & Health Care, Faculty of Population Health Sciences, University College LondonDepartment of Pathology, The First Affiliated Hospital of Soochow UniversityDepartment of Genetics, School of Basic Medical Sciences, Suzhou Medical College of Soochow UniversityAbstract Cyclic AMP-dependent protein kinase A (PKA) is recognized for its pivotal involvement in various cancer types, with Protein Kinase Inhibitor Beta (PKIB) serving as an endogenous inhibitor that curtails PKA activity. Despite the documented escalation of PKIB expression in several malignancies, a comprehensive understanding of its precise mechanistic implications in human cancers remains elusive. This investigation is centered on bladder cancer (BLCA), unveiling an augmented expression of PKIB concomitant with heightened BLCA cell proliferation, migration, and invasion in vitro and augmented tumorigenic potential in an in vivo model. Mechanistically, PKIB disrupts PKA kinase activity, thereby resulting in diminished phosphorylation of the substrate target protein HSP27 at serine 15, 78, and 82. Additionally, the transcription factor MYCN exhibits an affinity for the PKIB promoter, leading to its enhanced expression in the context of BLCA. These findings reveal the oncogenic proclivity of PKIB and introduce a novel signalling pathway in BLCA, providing valuable insights into potential therapeutic targets for precise intervention.https://doi.org/10.1038/s41419-025-07814-7 |
| spellingShingle | Xiaolong Liu Xiaoyu Yin Feng Yuan Shiqing Li Fei Xiao Feng Zhou Xudong Pan Yatfaat Ho Shuo Dong Duan Xu Yunqing Ma Zhengding Cao Zhe Lei Yi Sun PKIB facilitates bladder cancer proliferation and metastasis through mediation of HSP27 phosphorylation by PKA Cell Death and Disease |
| title | PKIB facilitates bladder cancer proliferation and metastasis through mediation of HSP27 phosphorylation by PKA |
| title_full | PKIB facilitates bladder cancer proliferation and metastasis through mediation of HSP27 phosphorylation by PKA |
| title_fullStr | PKIB facilitates bladder cancer proliferation and metastasis through mediation of HSP27 phosphorylation by PKA |
| title_full_unstemmed | PKIB facilitates bladder cancer proliferation and metastasis through mediation of HSP27 phosphorylation by PKA |
| title_short | PKIB facilitates bladder cancer proliferation and metastasis through mediation of HSP27 phosphorylation by PKA |
| title_sort | pkib facilitates bladder cancer proliferation and metastasis through mediation of hsp27 phosphorylation by pka |
| url | https://doi.org/10.1038/s41419-025-07814-7 |
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