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Review
. 2021 Sep 19;13(18):4696.
doi: 10.3390/cancers13184696.

Prostate Cancer-Focus on Cholesterol

Lucija Škara  1   2   3 , Ana Huđek Turković  4 , Ivan Pezelj  5 , Alen Vrtarić  6 , Nino Sinčić  1   2   3 , Božo Krušlin  3   7   8 , Monika Ulamec  2   3   7   8
Affiliations
Review

Prostate Cancer-Focus on Cholesterol

Lucija Škara et al. Cancers (Basel). .

Abstract

Prostate cancer (PC) is the most common malignancy in men. Common characteristic involved in PC pathogenesis are disturbed lipid metabolism and abnormal cholesterol accumulation. Cholesterol can be further utilized for membrane or hormone synthesis while cholesterol biosynthesis intermediates are important for oncogene membrane anchoring, nucleotide synthesis and mitochondrial electron transport. Since cholesterol and its biosynthesis intermediates influence numerous cellular processes, in this review we have described cholesterol homeostasis in a normal cell. Additionally, we have illustrated how commonly deregulated signaling pathways in PC (PI3K/AKT/MTOR, MAPK, AR and p53) are linked with cholesterol homeostasis regulation.

Keywords: AR; PTEN; SREBP2; cholesterol; mTOR: MAP; p53; prostate cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
SREBP2 activation and regulation in physiologically normal cell. Hexagons indicate points of influence by commonly aberrant pathways in PC. Receptor tyrosine kinase (RTK); androgen receptor (AR); glycogen synthase kinase 3 (GSK3), high-density lipoprotein (HDL); low-density lipoprotein (LDL); low-density lipoprotein receptor (LDLR); ATP-binding cassette transporter A1 (ABCA1); ATP-binding cassette transporter G1 (ABCG1); scavenger receptor class B member 1 (SR-B1); insulin-induced gene (INSIG); SREBP cleavage-activating protein (SCAP); site-1 protease (S1P); site-2 protease (S2P); sterol regulatory element–binding protein-2 (SREBP2); sterol response element (SRE). Created with BioRender.com (accessed on 5 September 2021).
Figure 2
Figure 2
Cholesterol biosynthesis intermediates and products support prostate cancer growth. Enzymes involved in de novo cholesterol synthesis are indicated in orange. Acetyl-CoA acetyltransferase 2 (ACAT2), 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), mevalonate kinase (MVK), phosphomevalonate kinase (PMK), diphospho-mevalonate decarboxylase(MDD), Isopentenyl-pyrophosphate isomerase (IPP), farnesyl-diphosphate synthase (FDPS), squalene synthase (SQS), squalene monooxygenase(SQLE), sterol regulatory element–binding protein-2 (SREBP2), sterol response element (SRE), isoprenyl-cysteine carboxyl methyltransferase (ICMT). Created with BioRender.com (accessed on 5 September 2021).
See this image and copyright information in PMC

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