Multi-omics and pathway analysis identify potential roles for tumour n-acetyl
aspartate accumulation in murine models of castration resistant prostate cancer (original) (raw)
Salji, M. J. et al. (2022) Multi-omics and pathway analysis identify potential roles for tumour n-acetyl aspartate accumulation in murine models of castration resistant prostate cancer.iScience, 25(4), 104056. (doi: 10.1016/j.isci.2022.104056) (PMID:35345457) (PMCID:PMC8957019)
Abstract
Castration-resistant prostate cancer (CRPC) is incurable and remains a significant worldwide challenge (Oakes and Papa, 2015). Matched untargeted multi-level omic datasets may reveal biological changes driving CRPC, identifying novel biomarkers and/or therapeutic targets. Untargeted RNA sequencing, proteomics, and metabolomics was performed on xenografts derived from three independent sets of hormone naïve and matched CRPC human cell line models of local, lymph node and bone metastasis grown as murine orthografts. Collectively, we tested the feasibility of muti-omics analysis on models of CRPC in revealing pathways of interest for future validation investigation. Untargeted metabolomics revealed NAA and NAAG commonly accumulating in CRPC across three independent models and proteomics showed upregulation of related enzymes, namely N-Acetylated Alpha-Linked Acidic Dipeptidases (FOLH1/NAALADL2). Based on pathway analysis integrating multiple omic levels we hypothesise that increased NAA in CRPC may be due to upregulation of NAAG hydrolysis via NAALADLases providing a pool of Acetyl Co-A for upregulated sphingolipid metabolism and a pool of glutamate and aspartate for nucleotide synthesis during tumour growth.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by the Medical Research Council Clinical Research Training Fellowship awarded to MS (MR/L017997/1) and CRUK Beatson Institute core funding (C596/A31287) and CRUK core group awarded to HYL (A15151) and SZ (A29800). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Lilla, Dr Sergio and Zanivan, Professor Sara and Patel, Dr Rachana and Daly, Dr Ronan and Leung, Professor Hing and Van Den Broek, Mr Niels and Salji, Dr Mark and Sumpton, Mr David and Däbritz, Jan and Repiscak, Dr Peter |
| Authors: | Salji, M. J., Blomme, A., Däbritz, J. H. M., Repiscak, P., Lilla, S., Patel, R., Sumpton, D., Van Den Broek, N. J. F., Daly, R., Zanivan, S., and Leung, H. Y. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | iScience |
| Publisher: | Elsevier (Cell Press) |
| ISSN: | 2589-0042 |
| ISSN (Online): | 2589-0042 |
| Published Online: | 11 March 2022 |
| Copyright Holders: | Copyright © 2022 The Authors |
| First Published: | First published in iScience 25(4): 104056 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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Funder and Project Information
Quantitative proteomic analysis of castrate-resistant prostate cancer
Hing Leung
MR/L017997/1
Institute of Cancer Sciences
Deposit and Record Details
| ID Code: | 265614 |
|---|---|
| Depositing User: | Ms Jacqui Brannan |
| Datestamp: | 18 Mar 2022 11:16 |
| Last Modified: | 07 Apr 2025 00:33 |
| Date of acceptance: | 8 February 2022 |
| Date of first online publication: | 11 March 2022 |
| Date Deposited: | 21 February 2022 |
| Data Availability Statement: | No |