Short-Chain Fatty Acids as Therapeutic Agents in Colon Malignancies

Orchestral role of lipid metabolic reprogramming in T-cell malignancy

“…The upregulation of ACC1/2, ACSS, and ACLY has been observed in many cancer types ( 84 ) Interestingly, ACLY is also involved in nuclear dynamics by providing acetyl CoA for histone acetylation after their nuclear translocation ( 85 ). The FASN catalyzes the condensation of small precursor moieties into 16-carbon long fatty acid palmitate ( 86 , 87 ). The fatty acid molecules synthesized by FASN activity provide a significant fraction of cellular lipid content ( 87 ).…”

“…The FASN catalyzes the condensation of small precursor moieties into 16-carbon long fatty acid palmitate ( 86 , 87 ). The fatty acid molecules synthesized by FASN activity provide a significant fraction of cellular lipid content ( 87 ). The FA further undergoes conversions including elongation and desaturation.…”

“…SUMOylation of FASN can prevent its degradation ( 88 ). Moreover, the upregulation of HDAC3 maintains the deacetylated form of FASN in hepatic cancer cells ( 34 , 72 , 87 ). Otherwise, acetylation of FASN by KAT8 (lysine acetyl transferase 8) makes it susceptible to ubiquitin ligation and degradation ( 90 ).…”

“…Otherwise, acetylation of FASN by KAT8 (lysine acetyl transferase 8) makes it susceptible to ubiquitin ligation and degradation ( 90 ). Proteasomal degradation of FASN is also prevented by a mutation in ubiquitin ligase speckle-type POZ protein in prostate cancer cells ( 87 , 91 ).…”

“…Various mechanisms are reported to be upregulated for lipid uptake in cancer cells ( 87 ). Majorly, the uptake of free FA is carried out by CD36 (fatty acid translocase) or fatty acid transport proteins (FATPs) ( 45 , 87 ).…”