Inhibition on JNK Mimics Silencing of Wnt-11 Mediated Cellular Response in Androgen-Independent Prostate Cancer Cells
by
Elif Damla Arisan 1
, Ozge Rencuzogullari 2, Buse Keskin 2, Guy H. Grant 3 and 
Pinar Uysal-Onganer 4,*
Elif Damla Arisan 1, Ozge Rencuzogullari 2, Buse Keskin 2, Guy H. Grant 3 and Pinar Uysal-Onganer 4,*
1
Gebze Technical University, Institute of Biotechnology, 41400 Gebze-Kocaeli, Turkey
2
Istanbul Kultur University, Department of Molecular Biology and Genetics, Atakoy Campus, 34156 Istanbul, Turkey
3
School of Life Sciences, University of Bedfordshire, Park Square, Luton LU1 3JU, UK
4
Cancer Research Group, School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK
*
Author to whom correspondence should be addressed.
Biology 2020, 9(7), 142; https://doi.org/10.3390/biology9070142
Received: 20 April 2020 / Revised: 10 June 2020 / Accepted: 25 June 2020 / Published: 27 June 2020
(This article belongs to the Special Issue The regulators of metastasis related signalling targets in cancer cells)
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.
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MDPI and ACS Style
Arisan, E.D.; Rencuzogullari, O.; Keskin, B.; Grant, G.H.; Uysal-Onganer, P. Inhibition on JNK Mimics Silencing of Wnt-11 Mediated Cellular Response in Androgen-Independent Prostate Cancer Cells. Biology 2020, 9, 142.
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