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Article

SWATH-MS Based Proteomic Profiling of Prostate Cancer Cells Reveals Adaptive Molecular Mechanisms in Response to Anti-Androgen Therapy

1
Faculty of Health, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4059, Australia
2
Australian Prostate Cancer Research Centre-Queensland (APCRC-Q), Translational Research Institute, Queensland University of Technology, Brisbane, QLD 4012, Australia
*
Author to whom correspondence should be addressed.
Academic Editors: Udayan Guha and Xu Zhang
Cancers 2021, 13(4), 715; https://doi.org/10.3390/cancers13040715
Received: 15 December 2020 / Revised: 15 January 2021 / Accepted: 4 February 2021 / Published: 9 February 2021
(This article belongs to the Special Issue Proteomics in Cancer)
Androgen targeted therapy has been foundational in the management of advanced prostate cancer. Nevertheless, responses to the therapy are found to be seldom sustained, in which patients develop resistance and progress to a lethal and incurable castration-resistance stage. Therefore, comprehensive understanding of the molecular basis of treatment induced cellular responses is required to circumvent molecular mechanisms driving castration-resistance. Using an advanced, robust quantitative proteomic analysis, we profiled the prostate cancer cell proteome induced by the two AR antagonists/anti-androgens, Bicalutamide and Enzalutamide. We highlighted key molecular signatures and cellular pathways that provide insights into the anti-androgen induced adaptive cellular programming in prostate cancer cells. Targeting these molecules and associated pathways might be useful in developing novel therapeutic approaches and/or as biomarkers of predicting prostate cancer treatment response.
Prostate cancer (PCa) is the second most common cancer affecting men worldwide. PCa shows a broad-spectrum heterogeneity in its biological and clinical behavior. Although androgen targeted therapy (ATT) has been the mainstay therapy for advanced PCa, it inevitably leads to treatment resistance and progression to castration resistant PCa (CRPC). Thus, greater understanding of the molecular basis of treatment resistance and CRPC progression is needed to improve treatments for this lethal phenotype. The current study interrogated both proteomics and transcriptomic alterations stimulated in AR antagonist/anti-androgen (Bicalutamide and Enzalutamide) treated androgen-dependent cell model (LNCaP) in comparison with androgen-independent/castration-resistant cell model (C4-2B). The analysis highlighted the activation of MYC and PSF/SFPQ oncogenic upstream regulators in response to the anti-androgen treatment. Moreover, the study revealed anti-androgen induced genes/proteins related to transcription/translation regulation, energy metabolism, cell communication and signaling cascades promoting tumor growth and proliferation. In addition, these molecules were found dysregulated in PCa clinical proteomic and transcriptomic datasets, suggesting their potential involvement in PCa progression. In conclusion, our study provides key molecular signatures and associated pathways that might contribute to CRPC progression despite treatment with anti-androgens. Such molecular signatures could be potential therapeutic targets to improve the efficacy of existing therapies and/or predictive/prognostic value in CRPC for treatment response. View Full-Text
Keywords: prostate cancer; proteomics; transcriptomics; anti-androgen therapy; bicalutamide; enzalutamide prostate cancer; proteomics; transcriptomics; anti-androgen therapy; bicalutamide; enzalutamide
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MDPI and ACS Style

Liyanage, C.; Malik, A.; Abeysinghe, P.; Clements, J.; Batra, J. SWATH-MS Based Proteomic Profiling of Prostate Cancer Cells Reveals Adaptive Molecular Mechanisms in Response to Anti-Androgen Therapy. Cancers 2021, 13, 715. https://doi.org/10.3390/cancers13040715

AMA Style

Liyanage C, Malik A, Abeysinghe P, Clements J, Batra J. SWATH-MS Based Proteomic Profiling of Prostate Cancer Cells Reveals Adaptive Molecular Mechanisms in Response to Anti-Androgen Therapy. Cancers. 2021; 13(4):715. https://doi.org/10.3390/cancers13040715

Chicago/Turabian Style

Liyanage, Chamikara, Adil Malik, Pevindu Abeysinghe, Judith Clements, and Jyotsna Batra. 2021. "SWATH-MS Based Proteomic Profiling of Prostate Cancer Cells Reveals Adaptive Molecular Mechanisms in Response to Anti-Androgen Therapy" Cancers 13, no. 4: 715. https://doi.org/10.3390/cancers13040715

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