27-hydroxycholesterol: A novel player in molecular carcinogenesis of breast and prostate cancer. (October 2017)

• Record Type: Journal Article
• Authors: Marwarha, Gurdeep; Raza, Shaneabbas; Hammer, Kimberly; Ghribi, Othman
• Is Part Of: Chemistry and physics of lipids. Volume 207(2017)Part B
• Page Start: 108
• Page End: 126
• Publication Date: 2017-10
• Subjects: 27-OHC 27-hydroxycholesterol -- ADT androgen deprivation therapy -- AR androgen receptor -- ATF4 Activating Transcription Factor 4 -- ATF6 Activating Transcription Factor 6 -- C/EBP CCAAT / Enhancer binding proteins -- CHOP C/EBP homologous protein -- CIP2A cancerous inhibitor of PP2A -- COP cholesterol oxidation products -- CTCF CCCTC-binding transcription factor -- CRPC castrate-resistant prostate cancer -- CSC cancer stem cells -- CYP27A1 sterol 27-hydroxylase -- CYP7B1 oxysterol 7α-hydroxylase -- DNL de novo lipogenesis -- DDIT3 DNA-damage-inducible transcript 3 -- DHEA dehydroepiandrosterone -- ER estrogen receptor -- ERE estrogen response elements -- EMT epithelial-mesenchymal transition -- ERK extracellular signal regulated kinase-1/mitogen activated protein kinase 3 -- FGF-1 fibroblast growth factor-1 -- FAPα fibroblast activation protein alpha -- FBW7 F-box and WD repeat domain containing 7 -- FXR Farnesoid X receptor -- G9a histone-lysine N-methyltransferase -- GADD153 growth arrest and DNA damage-inducible protein -- HK hexokinases -- HIF1α hypoxia inducible factor 1 alpha -- HP1 heterochromatin protein 1 -- IGF1 insulin-like growth factor 1 -- IRE1α inositol requiring enzyme 1 alpha -- JNK cJun N-terminal kinase -- LXR liver X receptor -- MDM2 mouse double minute 2 protein -- MCP1 monocyte chemotactic protein 1 -- mCRPC metastatic castrate resistant prostate cancer -- MIP1β monocyte inflammatory protein 1β -- MMP matrix metalloproteinase -- NEdT neuroendocrine transdifferentiation -- NF-κB nuclear factor of kappa-light-polypeptide gene enhancer of activated B cells -- PCa prostate cancer -- PERK protein kinase R (PKR)-like endoplasmic reticulum kinase -- PFK1 phosphofructokinase 1 -- PFK2 phosphofructokinase 2 -- PP2A protein phosphatase 2A -- Ptc patched -- RXR retinoid X receptor -- SCP1 small C-terminal domain phosphatase 1 -- SERM selective estrogen receptor modulator -- Shh sonic hedgehog -- SKP2 S-phase kinase-associated protein 2 -- Smo smoothened -- SREBP sterol regulatory element-binding protein -- StAR steroidogenic acute regulatory protein 1 -- STAT3 signal transducer and activator of transcription 3 -- sXBP1 spliced X-box binding protein 1 -- TISC tumor initiating cancer stem cells -- TLR4 toll like receptor-4 -- TNBC triple negative breast cancer -- TNFα tumor necrosis factor alpha -- UPR unfolded protein response -- VDR Vitamin D receptor -- VEGFα Vascular Endothelial Growth Factor alpha; 27-hydroxycholesterol -- cholesterol -- breast cancer -- prostate cancer -- estrogen receptor -- Liver X receptor; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipids; Periodicals; Electronic journals; 547.77
• DOI: 10.1016/j.chemphyslip.2017.05.012
• Languages: English
• ISSNs: 0009-3084

Abstract

Highlights: 27-OHC is a SERM with potential implications in hormonal cancers. 27-OHC exacerbates ER+ breast cancer. 27-OHC increases cell proliferation in prostate cells. 27-OHC is a novel risk factor in hormonal cancers. Abstract: Several studies have suggested an etiological role for hypercholesterolemia in the pathogenesis of breast cancer and prostate cancer (PCa). However, the molecular mechanisms that underlie and mediate the hypercholesterolemia-fostered increased risk for breast cancer and PCa are yet to be determined. The discovery that the most abundant cholesterol oxidized metabolite in the plasma, 27 hydroxycholesterol (27-OHC), is a selective estrogen receptor modulator (SERM) and an agonist of Liver X receptors (LXR) partially fills the void in our understanding and knowledge of the mechanisms that may link hypercholesterolemia to development and progression of breast cancer and PCa. The wide spectrum and repertoire of SERM and LXR-dependent effects of 27-OHC in the context of all facets and aspects of breast cancer and prostate cancer biology are reviewed in this manuscript in a very comprehensive manner. This review highlights recent findings pertaining to the role of 27-OHC in breast cancer and PCa and delineates the signaling mechanisms involved in the governing of different facets of tumor biology, that include tumor cell proliferation, epithelial-mesenchymal transition (EMT), as well as tumor cell invasion, migration, and metastasis. We also discuss the limitations of contemporary studies and lack of our comprehension of the entire gamut of effects exerted by 27-OHC that may be relevant to the pathogenesis of breast cancer and PCa. We unveil and propose potential future directions of research that may further our understanding of the role of 27-OHC in breast cancer and PCa and help design therapeutic interventions against endocrine therapy-resistant breast cancer and PCa.