Inhibition of guanosine monophosphate synthetase ( GMPS ) blocks glutamine metabolism and prostate cancer growth

Inhibition of guanosine monophosphate synthetase ( GMPS ) blocks glutamine metabolism and prostate cancer growth.

Full text not available from this repository.
Item Type: Article
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

Actions (login required)

View Item View Item