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Inhibition on JNK mimics silencing of Wnt-11 mediated cellular response in androgen-independent prostate cancer cells

  • Elif Damla Arisan
    ,
  • Ozge Rencuzogullari
    ,
  • Buse Keskin
    ,
  • Guy Grant
    ,
  • Pinar Uysal-Onganer
Research Output: Contribution to journal Article Peer-review

Open access

Sustainable Development Goals

  • SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well

Abstract

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.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 142

Journal (Volume, Issue Number)

Biology (Volume 9, Issue 7)

Publication milestones

  • Accepted/In press - 25/06/2020
  • Published - 27/06/2020

Publication status

Published - 27/06/2020

External Publication IDs

  • handle.net: 10547/624510
  • Scopus: 85090723503

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