Abstract
Molecular reprogramming in response to chemotherapeutics leads to poor therapeutic outcomes for prostate cancer (PCa). In this study, we demonstrated that CXCR6-CXCL16 axis promotes DTX resistance and acts as a counter-defense mechanism. After CXCR6 activation, cell death in response to DTX was inhibited, and blocking of CXCR6 potentiated DTX cytotoxicity. Moreover, in response to DTX, PCa cells expressed higher CXCR6, CXCL16, and ADAM-10. Furthermore, ADAM-10-mediated release of CXCL16 hyper-activated CXCR6 signaling in response to DTX. Activation of CXCR6 resulted in increased GSK-3β, NF-κB, ERK1/2 phosphorylation, and survivin expression, which reduce DTX response. Finally, treatment of PCa cells with anti-CXCR6 monoclonal antibody synergistically or additively induced cell death with ∼1.5–4.5 fold reduction in the effective concentration of DTX. In sum, our data imply that co-targeting of CXCR6 would lead to therapeutic enhancement of DTX, leading to better clinical outcomes for PCa patients.
Original language | English |
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Pages (from-to) | 1-13 |
Number of pages | 13 |
Journal | Cancer Letters |
Volume | 454 |
DOIs | |
State | Published - Jul 10 2019 |
Bibliographical note
Funding Information:This study was supported in part by the funds ( SC1 CA180212 , UO1 CA179701 , R21 CA169716 and U54 CA118638 ) from NCI and Morehouse School of Medicine flow cytometry core supported by the NIMHD 5U54MD007602 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH . Authors would also like to acknowledge Don Hill, scientific editor of U54 partnership for editing this manuscript.
Funding Information:
This study was supported in part by the funds (SC1 CA180212, UO1 CA179701, R21 CA169716 and U54 CA118638) from NCI and Morehouse School of Medicine flow cytometry core supported by the NIMHD 5U54MD007602. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Authors would also like to acknowledge Don Hill, scientific editor of U54 partnership for editing this manuscript.
Publisher Copyright:
© 2019
Keywords
- ADAM10
- CXCL16
- CXCR6
- Docetaxel
- Prostate cancer
ASJC Scopus subject areas
- Oncology
- Cancer Research