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BUB1 drives the occurrence and development of bladder cancer by mediating the STAT3 signaling pathway
- Source :
- Journal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-17 (2021), Journal of Experimental & Clinical Cancer Research : CR
- Publication Year :
- 2021
- Publisher :
- BMC, 2021.
-
Abstract
- Background The incidence of bladder urothelial carcinoma (UC), a common malignancy of the urinary tract, is approximately three times higher in men than in women. High expression of the mitotic kinase BUB1 is associated with the occurrence and development of several cancers, although the relationship between BUB1 and bladder tumorigenesis remains unclear. Methods Using a microarray approach, we found increased BUB1 expression in human BCa. The association between BUB1 and STAT3 phosphorylation was determined through molecular and cell biological methods. We evaluated the impact of pharmacologic inhibition of BUB1 kinase activity on proliferation and BCa progression in vitro and in vivo. Results In this study, we found that BUB1 expression was increased in human bladder cancer (BCa). We further identified through a series of molecular and cell biological approaches that BUB1 interacted directly with STAT3 and mediated the phosphorylation of STAT3 at Ser727. In addition, the findings that pharmacologic inhibition of BUB1 kinase activity significantly suppressed BCa cell proliferation and the progression of bladder cancer in vitro and in vivo were further verified. Finally, we found that the BUB1/STAT3 complex promoted the transcription of STAT3 target genes and that depletion of BUB1 and mutation of the BUB1 kinase domain abrogated this transcriptional activity, further highlighting the critical role of kinase activity in the activation of STAT3 target genes. A pharmacological inhibitor of BUB1 (2OH-BNPP1) was able to significantly inhibit the growth of BCa cell xenografts. Conclusion This study showed that the BUB1 kinase drives the progression and proliferation of BCa by regulating the transcriptional activation of STAT3 signaling and may be an attractive candidate for therapeutic targeting in BCa.
- Subjects :
- Male
STAT3 Transcription Factor
Cancer Research
Cell
Proliferation
BUB1
Biology
Protein Serine-Threonine Kinases
medicine.disease_cause
Transfection
Stat3 Signaling Pathway
STAT3
Mice
medicine
Animals
Humans
Kinase activity
Phosphorylation
skin and connective tissue diseases
RC254-282
Cell Proliferation
Bladder cancer
Cell growth
Kinase
Research
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
medicine.anatomical_structure
Oncology
Urinary Bladder Neoplasms
Cancer research
Carcinogenesis
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 17569966
- Volume :
- 40
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental & Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....a69a449ae724cea000764afe43b06e10