Inhibition of guanosine monophosphate synthetase ( GMPS ) blocks glutamine metabolism and prostate cancer growth.
Full text not available from this repository.Item Type: | Article |
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Status: | Published |
Official URL: | https://doi.org/10.1002/path.5665 |
Journal or Publication Title: | The Journal of Pathology |
Volume: | 254 |
Number: | 2 |
Page Range: | pp. 135-146 |
Date: | 2021 |
Divisions: | Epigenetics and RNA Biology Gene and Stem Cell Therapy |
Depositing User: | General Admin |
Identification Number: | 10.1002/path.5665 |
ISSN: | 0022-3417 |
Date Deposited: | 10 Jun 2021 01:01 |
Abstract: | Glutamine is a critical nutrient in cancer; however, its contribution to purine metabolism in prostate cancer has not previously been determined. Guanosine monophosphate synthetase (GMPS) acts in the de novo purine biosynthesis pathway, utilizing a glutamine amide to synthesize the guanine nucleotide. This study demonstrates that GMPS mRNA expression correlates with Gleason score in prostate cancer samples, while high GMPS expression was associated with decreased rates of overall and disease/progression-free survival. Pharmacological inhibition or knockdown of GMPS significantly decreased cell growth in both LNCaP and PC-3 prostate cancer cells. We utilized [15 N-(amide)]glutamine and [U-13 C5 ]glutamine metabolomics to dissect the pathways involved and despite similar growth inhibition by GMPS knockdown, we show unique metabolic effects across each cell line. Using a PC-3 xenograft mouse model, tumor growth was also significantly decreased after GMPS knockdown, highlighting the importance of glutamine metabolism and providing support for GMPS as a therapeutic target in prostate cancer. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Keywords: GMPS; cell growth; glutamine; immunohistochemistry; knockdown; metabolism; metabolomics; prostate cancer; purine; xenograft. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
Creators: | Creators Email Wang, Qian UNSPECIFIED Guan, Yi Fang UNSPECIFIED Hancock, Sarah E UNSPECIFIED Wahi, Kanu UNSPECIFIED van Geldermalsen, Michelle UNSPECIFIED Zhang, Blake K UNSPECIFIED Pang, Angel UNSPECIFIED Nagarajah, Rajini UNSPECIFIED Mak, Blossom UNSPECIFIED Freidman, Natasha UNSPECIFIED Horvath, Lisa G UNSPECIFIED Turner, Nigel UNSPECIFIED Holst, Jeff UNSPECIFIED |
Last Modified: | 10 Jun 2021 01:01 |
URI: | https://eprints.centenary.org.au/id/eprint/987 |
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