Dysregulation of
fatty acid metabolism and de novo lipogenesis is a key driver of several
cancer types through highly
unsaturated fatty acid (HUFA) signaling precursors such as
arachidonic acid. The human chromosome 11q13 locus has long been established as the most frequently amplified in a variety of human
cancers. The
fatty acid desaturase genes (FADS1, FADS2 and FADS3) responsible for HUFA biosynthesis localize to the 11q12-13.1 region. FADS2 activity is promiscuous, catalyzing biosynthesis of several
unsaturated fatty acids by Δ6, Δ8, and Δ4 desaturation. Our main aim here is to review known and putative consequences of FADS2 dysregulation due to effects on the 11q13 locus potentially driving various
cancer types. FADS2 silencing causes synthesis of
sciadonic acid (5Z,11Z,14Z-20:3) in MCF7 cells and
breast cancer in vivo. 5Z,11Z,14Z-20:3 is structurally identical to
arachidonic acid (5Z,8Z,11Z,14Z-20:4) except it lacks the internal Δ8 double bond required for
prostaglandin and
leukotriene synthesis, among other
eicosanoids.
Palmitic acid has substrate specificity for both SCD and FADS2.
Melanoma, prostate, liver and
lung cancer cells insensitive to SCD inhibition show increased FADS2 activity and
sapienic acid biosynthesis. Elevated serum
mead acid levels found in
hepatocellular carcinoma patients suggest an unsatisfied demand for
arachidonic acid. FADS2
circular RNAs are at high levels in colorectal and
lung cancer tissues. FADS2
circular RNAs are associated with shorter overall survival in
colorectal cancer patients. The evidence thusfar supports an effort for future research on the role of FADS2 as a
tumor suppressor in a range of neoplastic disorders.