Regulation of mevalonate metabolism in cancer and immune cells

The mevalonate pathway is a highly conserved metabolic cascade and provides isoprenoid building blocks for the biosynthesis of vital cellular products such as cholesterol or prenyl pyrophosphates that serve as substrates for the posttranslational prenylation of numerous proteins. The pathway, which...

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Bibliographic Details
Published in:Biochimica et biophysica acta 2013-06, Vol.1831 (6), p.1009-1015
Main Authors: Thurnher, Martin, Gruenbacher, Georg, Nussbaumer, Oliver
Format: Article
Language:English
Subjects:
Animals
biosynthesis
Bisphosphonates
Caspase-1
cholesterol
Humans
Immunity, Innate - physiology
Innate immunity
isoprenoids
metastasis
Mevalonate
Mevalonic Acid - metabolism
monitoring
neoplasm cells
neoplasms
Neoplasms - metabolism
Neoplasms - pathology
Prenylation
proteins
pyrophosphates
Statins
therapeutics
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Summary:The mevalonate pathway is a highly conserved metabolic cascade and provides isoprenoid building blocks for the biosynthesis of vital cellular products such as cholesterol or prenyl pyrophosphates that serve as substrates for the posttranslational prenylation of numerous proteins. The pathway, which is frequently hyperactive in cancer cells, is considered an important target in cancer therapy, since prenylated members of the Ras superfamily are crucially involved in the control of proliferation, survival, invasion and metastasis of tumour cells. Upstream accumulation and downstream depletion of mevalonate pathway intermediates as induced for instance by aminobisphosphonates translate into different effects in cancer and immune cells. Thus, mevalonate pathway regulation can affect tumour biology either directly or exhibit indirect antitumour effects through stimulating cancer immune surveillance. The present review summarizes major effects of pharmacologic mevalonate pathway regulation in cancer and immune cells that may collaboratively contribute to the efficacy of cancer therapy. •p53 inactivation by mutation can enhance mevalonate metabolism in cancer cells.•Mevalonate pathway inhibitors may be able to reverse the malignant phenotype.•Mevalonate pathway inhibitors also have multifaceted immunostimulatory effects.•The mevalonate pathway is an important target in cancer therapy.
ISSN:1388-1981
0006-3002
1879-2618
DOI:10.1016/j.bbalip.2013.03.003