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

Abstract

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.