TWIST1, A novel androgen-regulated gene, is a target for NKX3-1 in prostate cancer cells

Eide, T. J.; Ramberg, Håkon; Glackin, Carlotta A.; Tindall, Donald J.; Taskén, Kristin Austlid

doi:10.1186/1475-2867-13-4

Cited by 32 publications

(25 citation statements)

References 19 publications

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“…As shown in Fig. 1A, endogenous Twist1 mRNA expression and protein were significantly induced by R1881 treatment in LNCaP cells, consistent with an earlier study reporting androgen regulation of Twist1 (Eide et al, 2013); LNCaP cells express AR and exhibit androgen-dependent cell growth (Horoszewicz et al, 1983). As expected (Jenster, 1999), androgen caused upregulation of AR in LNCaP cells (Fig.…”

Section: Androgen Treatment Induces Twist1 Expression In Androgendepesupporting

confidence: 89%

Androgen up-regulation of Twist1 gene expression is mediated by ETV1

Khatiwada¹,

Kannan²,

Malla³

et al. 2020

PeerJ

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Twist1, a basic helix-loop-helix transcription factor that regulates a number of genes involved in epithelial-to-mesenchymal transition (EMT), is upregulated in prostate cancer. Androgen regulation of Twist1 has been reported in a previous study. However, the mechanism of androgen regulation of the Twist1 gene is not understood because the Twist1 promoter lacks androgen receptor (AR)-responsive elements. Previous studies have shown that the Twist1 promoter has putative binding sites for PEA3 subfamily of ETS transcription factors. Our lab has previously identified Ets Variant 1 (ETV1), a member of the PEA3 subfamily, as a novel androgen-regulated gene that is involved in prostate cancer cell invasion through unknown mechanism. In view of these data, we hypothesized that androgen-activated AR upregulates Twist1 gene expression via ETV1. Our data confirmed the published work that androgen positively regulates Twist1 gene expression and further showed that this positive effect was directed at the Twist1 promoter. The positive effect of androgen on Twist1 gene expression was abrogated upon disruption of AR expression by siRNA or of AR activity by Casodex. More importantly, our data show that disruption of ETV1 leads to significant decrease in both androgen-mediated upregulation as well as basal level of Twist1, which we are able to rescue upon re-expression of ETV1. Indeed, we are able to show that ETV1 mediates the androgen upregulation of Twist1 by acting on the proximal region of Twist1 promoter. Additionally, our data show that Twist1 regulates prostate cancer cell invasion and EMT, providing a possible mechanism by which ETV1 mediates prostate cancer cell invasion. In conclusion, in this study we report Twist1 as an indirect target of AR and androgen regulation through ETV1.

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Section: Androgen Treatment Induces Twist1 Expression In Androgendepesupporting

confidence: 89%

Androgen up-regulation of Twist1 gene expression is mediated by ETV1

Khatiwada¹,

Kannan²,

Malla³

et al. 2020

PeerJ

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“…Note that not all pathways discussed in the manuscript are shown in this figure between these two proteins may exist. AR also upregulates NKX3-1, which represses TWIST1 via binding to the TWIST1 promoter [66]. Contrary to the above findings, which suggest that AR inhibits EMT, ectopic expression of AR in BPH-1 cells induces EMT, whereas knockdown of AR downregulates EMT markers [67], suggesting that AR may play a different role in culture conditions than within the tumor microenvironment.…”

Section: Signaling In Epcontrasting

confidence: 53%

Development of a Novel Method to Detect Prostate Cancer Circulating Tumor Cells (CTCs) Based on Epithelial-Mesenchymal Transition Biology

Armstrong¹

2014

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE December 2014 REPORT TYPE PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)Duke University Medical Durham, NC 27705 AND ADDRESS(ES) PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel CommandFort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTThe purpose of this DOD NIA is to develop a novel method to detect circulating tumor cells (CTCs) from men with metastatic castration resistant prostate cancer (CRPC) based on a range of CTC phenotypes. The novel method employs a nanoparticle polymersome that contains near-infrared emissive porphyrins and permits antibody conjugation for target engagement and flow sorting in the infrared spectrum for specificity. We are developing near infrared emissive polymersomes (NIR-EPs) that contain antibodies to EpCAM, N-cadherin, OB-cadherin, and PSMA which permit the isolation and enumeration ev vivo of CTCs bearing these antigens in the circulation of men with CRPC. These specialized CTC detection nanoparticles permit the isolation of specific CTC phenotypes including epithelial, mesenchymal, and prostate cancer specific targets. In year 2 we have continued to optimize the methodology and chemistry for the creation of these NIR-EPs, including chemical synthesis, antibody conjugation, optimal reagents and processing, positive and negative control cell applications, and methods for red cell lysis, leukocyte depletion, and flow sorting of CTCs in the infrared spectrum. Challenges have included specificity due to antibody affinity during conjugation. This work is ongoing in the Therien laboratory to provide a clinical reagent for the ex vivo capture and identification of CTCs without binding to leukocytes nonspecifically. A 6 month no cost extension was requested to continue this optimization process. 2 Many patients with metastatic PC, however, have undetectable CTCs, limiting clinical utility. We have identified epithelial-mesench...

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“…Twist 1 was found to bind to E-boxes, 5'-CANNTG-3', in the proximal promoter (-442 to +51 bp) and upstream regions (-539 to -974 bp and -1187 to -1589 bp) (Eide et al 2013). However, it has also been reported that androgens upregulate Twist 1 expression, observed in prostate cancer microarrays (Ngan et al 2009), and in LNCaP cells after 72 hours of treatment with the powerful androgen agonist R1881 (Eide et al 2013). These apparently contradictory findings appear to be due to the differing timescales used, with an initial downregulation of Twist 1 expression by increased NKX3-1 eventually being overcome by androgen upregulation.…”

Section: Androgens and The Process Of Epithelial Mesenchymal Transitionmentioning

confidence: 99%

Tissue control of androgen action: The ups and downs of androgen receptor expression

Hunter

Hay

Esswein

et al. 2018

Molecular and Cellular Endocrinology

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Please cite this article as: Hunter, I., Hay, C.W., Esswein, B., Watt, K., McEwan, I.J., Tissue control of androgen action: The ups and downs of androgen receptor expression, Molecular and Cellular Endocrinology (2017), doi: 10.1016/j.mce.2017 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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TWIST1, A novel androgen-regulated gene, is a target for NKX3-1 in prostate cancer cells

Cited by 32 publications

References 19 publications

Androgen up-regulation of Twist1 gene expression is mediated by ETV1

Androgen up-regulation of Twist1 gene expression is mediated by ETV1

Development of a Novel Method to Detect Prostate Cancer Circulating Tumor Cells (CTCs) Based on Epithelial-Mesenchymal Transition Biology

Tissue control of androgen action: The ups and downs of androgen receptor expression

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