Abstract
Hepatobiliary cancers are a collection of malignancies arising from liver and biliary tract cells. These cancers have high anatomical proximity, overlapping symptoms, and share common risk factors. Hepatobiliary cancers are generally rare and often lack effective treatment options due to late diagnoses and limited treatment efficacy. These cancers tend to be highly aggressive, which limits treatment options for patients, especially since diagnosis often occurs at later stages of disease progression. Chronic inflammation is the most significant risk factor for developing these malignancies. Inflammation alters cellular metabolism, which gives them unique metabolism characteristics that enhance their survival and increase malignancy. Acetyl-Coa-carboxylase (ACC) is a metabolic enzyme responsible for the carboxylation of acetyl-CoA (AC) into malonyl-CoA (MC). MC is used in de novo fatty acid synthesis, an upregulated process in human cancers. Acetyl-Coa-carboxylase 1 (ACC1), in particular, is the first rate-limiting step for de novo lipogenesis. Here we delve into the effect of ACC1 inhibition on the malignant phenotypes of hepatobiliary cancers. Our results showed that knockdown of ACC1 slowed proliferation and migration, reduced spheroid formation, and altered cell cycle progression and protein expression in hepatobiliary cancers. In conclusion, our study suggests that ACC1 may contribute to hepatobiliary cancers' malignancy and may be utilized as a therapeutic target for treating such diseases.