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Oncogene, volume 38, issue 6, pages 838-851

Reduced Arginyltransferase 1 is a driver and a potential prognostic indicator of prostate cancer metastasis

Birnbaum Michael D. 1
Zhao Ning 1
Moorthy Balaji T 1
Patel Devang M. 1
Kryvenko Oleksandr N 2, 3, 4
Heidman Laine 1
Kumar Akhilesh 1, 5
Morgan William M. 1
Ban Yuguang 6
Reis Isildinha M. 3, 6
Chen Xi 3, 6
Gonzalgo Mark L 2, 3
Jorda Merce 3, 4
Burnstein Kerry L. 1, 3
Zhang Fangliang 1, 3
1
 
Department of Molecular and Cellular Pharmacology, University of Miami, Miller School of Medicine, Miami, USA
2
 
Department of Urology, University of Miami Miller school of Medicine, Miami, USA
3
 
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, USA
4
 
Department of Pathology, University of Miami Miller School of Medicine, Miami, USA
6
 
Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, USA
Publication typeJournal Article
Publication date2018-09-03
Journal: Oncogene
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor8
ISSN09509232, 14765594
Cancer Research
Molecular Biology
Genetics
Abstract
Most prostate cancer cases remain indolent for long periods of time, but metastatic progression quickly worsens the prognosis and leads to mortality. However, little is known about what promotes the metastasis of prostate cancer and there is a lack of effective prognostic indicators, making it immensely difficult to manage options for treatment or surveillance. Arginyltransferase 1 (Ate1) is the enzyme mediating post-translational protein arginylation, which has recently been identified as a master regulator affecting many cancer-relevant pathways including stress response, cell cycle checkpoints, and cell migration/adhesion. However, the precise role of Ate1 in cancer remains unknown. In this study, we found the occurrence of metastasis of prostate cancer is inversely correlated with the levels of Ate1 protein and mRNA in the primary tumor. We also found that metastatic prostate cancer cell lines have a reduced level of Ate1 protein compared to non-metastatic cell lines, and that a depletion of Ate1 drives prostate cancer cells towards more aggressive pro-metastatic phenotypes without affecting proliferation rates. Furthermore, we demonstrated that a reduction of Ate1 can result from chronic stress, and that shRNA-reduced Ate1 increases cellular resistance to stress, and drives spontaneous and stress-induced genomic mutations. Finally, by using a prostate orthotropic xenograft mouse model, we found that a reduction of Ate1 was sufficient to enhance the metastatic phenotypes of prostate cancer cell line PC-3 in vivo. Our study revealed a novel role of Ate1 in suppressing prostate cancer metastasis, which has a profound significance for establishing metastatic indicators for prostate cancer, and for finding potential treatments to prevent its metastasis.

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Birnbaum M. D. et al. Reduced Arginyltransferase 1 is a driver and a potential prognostic indicator of prostate cancer metastasis // Oncogene. 2018. Vol. 38. No. 6. pp. 838-851.
GOST all authors (up to 50) Copy
Birnbaum M. D., Zhao N., Moorthy B. T., Patel D. M., Kryvenko O. N., Heidman L., Kumar A., Morgan W. M., Ban Y., Reis I. M., Chen X., Gonzalgo M. L., Jorda M., Burnstein K. L., Zhang F. Reduced Arginyltransferase 1 is a driver and a potential prognostic indicator of prostate cancer metastasis // Oncogene. 2018. Vol. 38. No. 6. pp. 838-851.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.1038/s41388-018-0462-2
UR - https://doi.org/10.1038%2Fs41388-018-0462-2
TI - Reduced Arginyltransferase 1 is a driver and a potential prognostic indicator of prostate cancer metastasis
T2 - Oncogene
AU - Birnbaum, Michael D.
AU - Zhao, Ning
AU - Moorthy, Balaji T
AU - Patel, Devang M.
AU - Kryvenko, Oleksandr N
AU - Heidman, Laine
AU - Kumar, Akhilesh
AU - Morgan, William M.
AU - Ban, Yuguang
AU - Reis, Isildinha M.
AU - Chen, Xi
AU - Gonzalgo, Mark L
AU - Jorda, Merce
AU - Burnstein, Kerry L.
AU - Zhang, Fangliang
PY - 2018
DA - 2018/09/03 00:00:00
PB - Springer Nature
SP - 838-851
IS - 6
VL - 38
PMID - 30177837
SN - 0950-9232
SN - 1476-5594
ER -
BibTex |
Cite this
BibTex Copy
@article{2018_Birnbaum
author = {Michael D. Birnbaum and Ning Zhao and Balaji T Moorthy and Devang M. Patel and Oleksandr N Kryvenko and Laine Heidman and Akhilesh Kumar and William M. Morgan and Yuguang Ban and Isildinha M. Reis and Xi Chen and Mark L Gonzalgo and Merce Jorda and Kerry L. Burnstein and Fangliang Zhang},
title = {Reduced Arginyltransferase 1 is a driver and a potential prognostic indicator of prostate cancer metastasis},
journal = {Oncogene},
year = {2018},
volume = {38},
publisher = {Springer Nature},
month = {sep},
url = {https://doi.org/10.1038%2Fs41388-018-0462-2},
number = {6},
pages = {838--851},
doi = {10.1038/s41388-018-0462-2}
}
MLA
Cite this
MLA Copy
Birnbaum, Michael D., et al. “Reduced Arginyltransferase 1 is a driver and a potential prognostic indicator of prostate cancer metastasis.” Oncogene, vol. 38, no. 6, Sep. 2018, pp. 838-851. https://doi.org/10.1038%2Fs41388-018-0462-2.
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