bioRxiv Science⌕ Search

Biology subjects

Scott, J. S.

Publications and source records attributed to Scott, J. S..

2 recordsLinked to original sources

Cis-vaccenic acid is a key product of stearoyl-CoA desaturase 1 and a critical oncogenic factor in prostate cancer

Altered monounsaturated fatty acid (MUFA) metabolism is a hallmark of oncogenic transformation. Recently, the MUFA cis-vaccenic acid (cVA) was identified as a putative regulator of prostate cancer cell viability. cVA production requires the activity of stearoyl CoA desaturase 1 (SCD1), an enzyme frequently dysregulated in cancer, but the role of cVA in regulating cancer cell phenotypes has not been extensively explored, compared with the more commonly studied product and structural isomer of cVA, oleic acid. Here, we utilised SCD1 inhibition to study the effects of cVA in prostate cancer cells. We found that cVA consistently rescues reductions in cell viability due to SCD1 inhibition and promotes cell growth under normal conditions, thereby identifying cVA as an important and previously unrecognised product of SCD1 in prostate cancer. More broadly, we demonstrate that individual MUFA species exert a diverse range of influence on oncogenic phenotypes, highlighting a need to more precisely characterise the lipidome of cancer cells to understand the molecular pathology of the disease.

cell biology↗

OzFAD: Ozone-enabled fatty acid discovery reveals unexpected diversity in the human lipidome

Fatty acid isomers are responsible for an under-reported lipidome diversity across all kingdoms of life. Isomers of unsaturated fatty acid are often masked in contemporary analysis by incomplete separation and the absence of sufficiently diagnostic methods for structure elucidation. Here, we introduce a comprehensive workflow to discover new unsaturated fatty acids through coupling liquid chromatography and mass spectrometry with gas-phase ozonolysis of double bonds. The workflow encompasses semi-automated data analysis and enables de novo identification in complex media including human plasma, cancer cell lines and human sebaceous wax (i.e., vernix caseosa). The targeted analysis including ozonolysis enables structural assignment over a dynamic range of five orders of magnitude, even in instances of incomplete chromatographic separation. Thereby we expand the number of identified plasma fatty acids two-fold, including non-methylene interrupted fatty acids. Detection, without prior knowledge, allows discovery of non-canonical double bond positions. Changes in relative isomer abundances reflect underlying perturbations in lipid metabolism.

molecular biology↗