Inhibition on JNK mimics silencing of Wnt-11 mediated cellular response in androgen-independent prostate cancer cells
Affiliation
Gebze Technical UniversityIstanbul Kultur University
University of Bedfordshire
University of Westminster
Issue Date
2020-06-27
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Prostate cancer (PCa) is one of the most common cancers among men, and one of the leading causes of cancer death for men. The c-Jun N-terminal kinase (JNK) pathway is required for several cellular functions, such as survival, proliferation, differentiation, and migration. Wnt-11, a member of the Wnt family, has been identified for its upregulation in PCa; however, downstream signalling of Wnt-11 remains to be fully characterized. In this study, we investigated the role of the JNK pathway as a potential downstream factor for Wnt-11 signalling. For this purpose, LNCaP, DU145, and PC-3 PCa cells and normal epithelial PNT1A cells were treated with a specific JNK kinase inhibitor: JNKVIII. Our results showed that JNK inhibition decreased mitochondrial membrane potential and promoted cell death in a cell type-dependent manner. We found that JNK inhibition led to an increase in autophagy and prevented epithelial-mesenchymal transition (EMT) in independently growing androgen cells. JNK inhibition and the silencing of Wnt-11 showed similar responses in DU145 and PC-3 cells and decreased metastasis-related biomarkers, cell migration, and invasion. Overall, our results suggest that JNK signalling plays a significant role in the pathophysiology of PCa by mediating Wnt-11 induced signals. Our data highlights that both the JNK pathway and Wnt-11 could be a useful therapeutic target for the combinatory application of current PCa.Citation
Arisan ED, Rencuzogullari O, Keskin B, Grant GH, Uysal-Onganer P (2020) 'Inhibition on JNK mimics silencing of Wnt-11 mediated cellular response in androgen-independent prostate cancer cells', Biology, 9 (7), pp.142-.Publisher
MDPIJournal
BiologyPubMed ID
32605008Additional Links
https://www.mdpi.com/2079-7737/9/7/142Type
ArticleLanguage
enISSN
2079-7737EISSN
2079-7737ae974a485f413a2113503eed53cd6c53
10.3390/biology9070142
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