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Myc-dependent purin...
Myc-dependent purine biosynthesis affects nucleolar stress and therapy response in prostate cancer.
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Barfeld, Stefan J (författare)
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Fazli, Ladan (författare)
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- Persson, Margareta (författare)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine
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Marjavaara, Lisette (författare)
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Urbanucci, Alfonso (författare)
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Kaukoniemi, Kirsi M (författare)
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Rennie, Paul S (författare)
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- Ceder, Yvonne (författare)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine
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Chabes, Andrei (författare)
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Visakorpi, Tapio (författare)
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Mills, Ian G (författare)
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(creator_code:org_t)
- 2015-03-30
- 2015
- Engelska.
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:14, s. 12587-12602
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http://www.oncotarge...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Barfeld, Stefan ...
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Fazli, Ladan
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Persson, Margare ...
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Marjavaara, Lise ...
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Urbanucci, Alfon ...
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Kaukoniemi, Kirs ...
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visa fler...
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Rennie, Paul S
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Ceder, Yvonne
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Chabes, Andrei
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Visakorpi, Tapio
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Mills, Ian G
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Artiklar i publikationen
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Oncotarget
- Av lärosätet
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Lunds universitet