Activated androgen receptor promotes bladder cancer metastasis via Slug mediated epithelial-mesenchymal transition

Jing, Yifeng; Cui, Di; Guo, Wei; Jiang, Junwei; Jiang, Bo; Lu, Youyi; Zhao, Wei; Wang, Xiaohai; Jiang, Qi; Han, Bangmin; Xia, Shujie

doi:10.1016/j.canlet.2014.03.018

Cited by 81 publications

(70 citation statements)

References 42 publications

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“…12,[14][15][16][17][18][19][20] In accordance with our current findings in UUTUCs, significant decreases in the ARpositive rate have been reported in BCs, compared with nonneoplastic urothelial tissues. [14][15][16] In contrast, 2 other studies showed no AR expression in normal bladder urothelium.…”

Section: Discussionsupporting

confidence: 80%

Expression of steroid hormone receptors and its prognostic significance in urothelial carcinoma of the upper urinary tract

Kashiwagi

Fujita

Yamaguchi

et al. 2016

Cancer Biology & Therapy

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To assess the expression status of steroid hormone receptors in upper urinary tract urothelial carcinoma (UUTUC), we immunohistochemically stained for androgen receptor (AR), estrogen receptor-a (ERa), ERb, glucocorticoid receptor (GR), and progesterone receptor (PR) in 99 UUTUC specimens and paired nonneoplastic urothelial tissues. AR/ERa/ERb/GR/PR was positive in 20%/18%/62%/63%/16% of tumors, which was significantly lower (except PR) than in benign urothelial tissues [57% (. There were no significant associations between each receptor expression pattern and histopathological characteristic of the tumors including tumor grade/ stage. Kaplan-Meier and log-rank tests revealed no significant prognostic value of each receptor expression in these 99 patients. However, patients with UUTUC positive for either ERa or PR had a significantly higher risk of disease-specific mortality (P D 0.025), compared with those with UUTUC negative for both. PR positivity alone in pT3 or pT4 tumors was also strongly associated with the risk of disease-specific mortality (P D 0.040). Multivariate analysis further identified the expression of ERa and/or PR as a strong predictor for disease-specific mortality in the entire cohort of the patients (hazard ratio, 2.434; P D 0.037). Thus, in accordance with previous observations in bladder specimens, significant decreases in the expression of AR/ERa/ERb/GR in UUTUC, compared with that in non-neoplastic urothelium, were observed. Meanwhile, the negativity of both ERa and PR in UUTUC as well as the negativity of PR alone in deeply invasive tumor was suggested to serve as a prognosticator.

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Section: Discussionsupporting

confidence: 80%

Expression of steroid hormone receptors and its prognostic significance in urothelial carcinoma of the upper urinary tract

Kashiwagi

Fujita

Yamaguchi

et al. 2016

Cancer Biology & Therapy

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“…Others have found that androgen stimulation of AR positive bladder cancer cells promoted a mesenchymal phenotype, migration and invasion in vitro, and metastasis in vivo (Jing et al 2014). Furthermore, it was determined that this effect was mediated via canonical Wnt signaling which activates Slug (Jing et al 2014). These data were supported in a subsequent study that demonstrated that AR mediated promotion of migration (Jitao et al 2014).…”

Section: The Role Of the Ar In Bladder Cancer Invasion And Angiogenesissupporting

confidence: 72%

“…In cell culture studies, an AR knockdown resulted in decreased CD24 expression and cell proliferation, while treatment with androgens increased CD24 levels, arguing that CD24 is androgen regulated in urothelial cells (Overdevest et al 2012). Others have found that androgen stimulation of AR positive bladder cancer cells promoted a mesenchymal phenotype, migration and invasion in vitro, and metastasis in vivo (Jing et al 2014). Furthermore, it was determined that this effect was mediated via canonical Wnt signaling which activates Slug (Jing et al 2014).…”

Section: The Role Of the Ar In Bladder Cancer Invasion And Angiogenesismentioning

confidence: 99%

“…In the context of prostate cancer, ADT has been shown to promote EMT (Sun et al 2012). Since studies suggest that the AR and androgen signaling promote EMT, migration, and invasion in bladder tumors and flutamide or an siRNA targeting the AR inhibits these responses, it is reasonable to hypothesize that ADT could be beneficial in the long term for certain patients (Jing et al 2014, Jitao et al 2014. However, identifying the patient cohort that would benefit from this intervention should be addressed prior to initiating such therapies.…”

Section: Therapeutic Potential Of Targeting the Ar In Bladder Cancermentioning

confidence: 99%

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The emerging role of the androgen receptor in bladder cancer

Lombard¹,

Mudryj²

2015

Endocrine-Related Cancer

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Men are three to four times more likely to get bladder cancer than women. The gender disparity characterizing bladder cancer diagnoses has been investigated. One hypothesis is that androgen receptor (AR) signaling is involved in the etiology and progression of this disease. Although bladder cancer is not typically described as an endocrine-related malignancy, it has become increasingly clear that AR signaling plays a role in bladder tumors. This review summarizes current findings regarding the role of the AR in bladder cancer. We discuss work demonstrating AR expression in bladder cancer and its role in promoting formation and progression of tumors. Additionally, we discuss the therapeutic potential of targeting the AR in this disease.

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“…Finally, data were available from five studies on AR expression and bladder cancer susceptibility (568 tumor cases vs. 523 normal controls), six studies on AR expression and tumor grade (387 low grade vs. 663 high grade cases), nine studies on AR expression and tumor stage (582 non-invasive vs. 712 invasive cases), five studies on AR expression and RFS (414 cases) and four studies on AR expression and PFS (319 cases). The essential information of the included studies was listed in Table I ( [8][9][10][11][19][20][21][22][23][24][25][26].…”

Section: Resultsmentioning

confidence: 99%

Expression and clinical significance of androgen receptor in bladder cancer: A meta-analysis

Chen

Liu

et al. 2017

Molecular and Clinical Oncology

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Abstract. Emerging evidence has demonstrated that androgen receptor (AR) is a promising therapeutic target for bladder cancer. However, the relationship between AR expression and its clinical significance remains controversial. The present in-depth meta-analysis aimed to investigate the correlation between AR expression and clinicopathological features, as well as prognostic value in bladder cancer. A systematic search was performed from PubMed, Web of Knowledge, Embase and the Cochrane Central Search Library by January 2017. The correlation between AR expression and tumor stage, tumor grade, recurrence free survival and progression free survival for patients with bladder cancer was evaluated. A total of 12 relevant studies with 1,652 patient samples were included. AR expression positively correlated with low tumor grade [odds ratio (OR), 1.95; 95% confidence interval (CI), 1.36-2.81], low tumor stage (OR, 2.06; 95% CI, 1.02-4.16) and low recurrence rate [hazard ratio (HR), 0.48; 95% CI, 0.31-0.75] in Caucasian patients. While, its expression had no significant impact on cancer susceptibility (OR, 1.62; 95% CI, P= 0.44) and progression-free survival (HR, 1.20; 95% CI, P=0.77). The present meta-analysis indicated that AR expression correlates with tumor grade, clinical stage and recurrence rates in the specified population and classification system.Further studies are required to determine the precise role of AR in bladder cancer.

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Activated androgen receptor promotes bladder cancer metastasis via Slug mediated epithelial-mesenchymal transition

Cited by 81 publications

References 42 publications

Expression of steroid hormone receptors and its prognostic significance in urothelial carcinoma of the upper urinary tract

Expression of steroid hormone receptors and its prognostic significance in urothelial carcinoma of the upper urinary tract

The emerging role of the androgen receptor in bladder cancer

Expression and clinical significance of androgen receptor in bladder cancer: A meta-analysis

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