Fatty Acid Desaturase-1 (FADS1) or
delta 5 desaturase (D5D) is a rate-limiting
enzyme involved in the biosynthesis of long-chain
polyunsaturated fatty acids (LC-PUFAs), i.e.,
arachidonic acid (ARA) and eicosapentaenoic (EPA). These LC-PUFAs and their metabolites play essential and broad roles in
cancer cell proliferation,
metastasis, and tumor microenvironment. However, the role of FADS1 in
cancers remains incompletely understood. Utilizing The
Cancer Genome Atlas (TCGA) database, we explored the role of FADS1 across different
cancer types using multiple bioinformatics and statistical tools. Moreover, we studied the impact of a FADS1 inhibitor (D5D-IN-326) on proliferation of multiple
cancer cell lines. We identified that FADS1 gene is a predictor for
cancer survival in multiple
cancer types. Compared to normal tissue, the
mRNA expression of FADS1 is significantly increased in primary
tumors while even higher in metastatic and recurrent
tumors. Mechanistically, pathway analysis demonstrated that FADS1 is associated with
cholesterol biosynthesis and cell cycle control genes. Interestingly, FADS1 expression is higher when TP53 is mutated.
Tumors with increased FADS1 expression also demonstrated an increased signatures of fibroblasts and macrophages infiltration among most
cancer types. Our in vitro assays showed that D5D-IN-326 significantly inhibited cell proliferation of kidney, colon, breast, and
lung cancer cell lines in a dose-dependent manner. Lastly, single nucleotide polymorphisms (SNPs) which are well-established expression quantitative trait loci (eQTLs) for FADS1 in normal human tissues are also significantly correlated with FADS1 expression in
tumors of multiple tissue types, potentially serving as a marker to stratify
cancer patients with high/low FADS1 expression in their
tumor tissue. Our study suggests that FADS1 plays multiple roles in
cancer biology and is potentially a novel target for precision
cancer treatment.