STAT3 and STAT5A are potential therapeutic targets in castration-resistant prostate cancer

Sambit K. Mohanty, Kader Yagiz, Dinesh Pradhan, Daniel J. Luthringer, Mahul Amin, Serhan Alkan, Bekir Cinar

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Mechanisms of castration-resistant prostate cancer (CRPC) are not well understood, thus hindering rational-based drug design. Activation of STAT3/5A, key components of the JAK/STAT pathway, is implicated in aggressive PC, yet their clinical relevance in CRPC remains elusive. Here, we evaluated the possible role of STAT3/5A in CRPC using immunological, quantitative mRNA expression profiling, and pharmacological methods. We observed a strong nuclear immunoreactivity for STAT3 and STAT5A in 93% (n=14/15) and 80% (n=12/15) of CRPC cases, respectively, compared with benign prostatic hyperplasia (BPH). We demonstrated that PC cells express varying levels of STAT3 and STAT5A transcripts. In addition, we demonstrate that pimozide, a psychotropic drug and an indirect inhibitor of STAT5, attenuated PC cells growth, and induced apoptosis in a dose-dependent manner. Furthermore, our analysis of the PC public data revealed that the STAT3/5A genes were frequently amplified in metastatic CRPC. These findings suggest that STAT3/5A potentially serves as a predictive biomarker to evaluate the therapeutic efficacy of a cancer drug targeting the JAK/STAT pathway. Since the JAK/STAT and AR pathways are suggested to be functionally synergistic, inhibition of the JAK/STAT signaling alone or together with AR may lead to a novel treatment modality for patients with advanced PC.

Original languageEnglish (US)
Pages (from-to)85997-86010
Number of pages14
JournalOncotarget
Volume8
Issue number49
DOIs
StatePublished - Oct 17 2017

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Castration
Prostatic Neoplasms
Pimozide
Therapeutics
Drug Design
Psychotropic Drugs
Prostatic Hyperplasia
Drug Delivery Systems
Biomarkers
Pharmacology
Apoptosis
Messenger RNA
Growth
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Mohanty, S. K., Yagiz, K., Pradhan, D., Luthringer, D. J., Amin, M., Alkan, S., & Cinar, B. (2017). STAT3 and STAT5A are potential therapeutic targets in castration-resistant prostate cancer. Oncotarget, 8(49), 85997-86010. https://doi.org/10.18632/oncotarget.20844

STAT3 and STAT5A are potential therapeutic targets in castration-resistant prostate cancer. / Mohanty, Sambit K.; Yagiz, Kader; Pradhan, Dinesh; Luthringer, Daniel J.; Amin, Mahul; Alkan, Serhan; Cinar, Bekir.

In: Oncotarget, Vol. 8, No. 49, 17.10.2017, p. 85997-86010.

Research output: Contribution to journalArticle

Mohanty, SK, Yagiz, K, Pradhan, D, Luthringer, DJ, Amin, M, Alkan, S & Cinar, B 2017, 'STAT3 and STAT5A are potential therapeutic targets in castration-resistant prostate cancer', Oncotarget, vol. 8, no. 49, pp. 85997-86010. https://doi.org/10.18632/oncotarget.20844
Mohanty, Sambit K. ; Yagiz, Kader ; Pradhan, Dinesh ; Luthringer, Daniel J. ; Amin, Mahul ; Alkan, Serhan ; Cinar, Bekir. / STAT3 and STAT5A are potential therapeutic targets in castration-resistant prostate cancer. In: Oncotarget. 2017 ; Vol. 8, No. 49. pp. 85997-86010.
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