Change search
ReferencesLink to record
Permanent link

Direct link
Myc-dependent purine biosynthesis affects nucleolar stress and therapy response in prostate cancer
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). (Andrei Chabes)
Show others and affiliations
2015 (English)In: OncoTarget, ISSN 1949-2553, Vol. 6, no 14, 12587-12602 p.Article in journal (Refereed) Published
Abstract [en]

The androgen receptor is a key transcription factor contributing to the development of all stages of prostate cancer (PCa). In addition, other transcription factors have been associated with poor prognosis in PCa, amongst which c-Myc (MYC) is a well-established oncogene in many other cancers. We have previously reported that the AR promotes glycolysis and anabolic metabolism; many of these metabolic pathways are also MYC-regulated in other cancers. In this study, we report that in PCa cells de novo purine biosynthesis and the subsequent conversion to XMP is tightly regulated by MYC and independent of AR activity. We characterized two enzymes, PAICS and IMPDH2, within the pathway as PCa biomarkers in tissue samples and report increased efficacy of established anti-androgens in combination with a clinically approved IMPDH inhibitor, mycophenolic acid (MPA). Treatment with MPA led to a significant reduction in cellular guanosine triphosphate (GTP) levels accompanied by nucleolar stress and p53 stabilization. In conclusion, targeting purine biosynthesis provides an opportunity to perturb PCa metabolism and enhance tumour suppressive stress responses.

Place, publisher, year, edition, pages
2015. Vol. 6, no 14, 12587-12602 p.
Keyword [en]
prostate, cancer, nucleotide, transcription, metabolism
National Category
Cell and Molecular Biology
URN: urn:nbn:se:umu:diva-101879ISI: 000359008200062PubMedID: 25869206OAI: diva2:805384
Available from: 2015-04-15 Created: 2015-04-15 Last updated: 2015-08-31Bibliographically approved

Open Access in DiVA

fulltext(17139 kB)78 downloads
File information
File name FULLTEXT01.pdfFile size 17139 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links


Search in DiVA

By author/editor
Marjavaara, LisetteChabes, Andrei
By organisation
Department of Medical Biochemistry and BiophysicsMolecular Infection Medicine Sweden (MIMS)
In the same journal
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 78 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 62 hits
ReferencesLink to record
Permanent link

Direct link