Diminishing acetyl-CoA carboxylase 1 attenuates CCA migration via AMPK-NF-κB-snail axis
4
Issued Date
2023-06-01
Resource Type
ISSN
09254439
eISSN
1879260X
Scopus ID
2-s2.0-85151505165
Pubmed ID
36972768
Journal Title
Biochimica et Biophysica Acta - Molecular Basis of Disease
Volume
1869
Issue
5
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biochimica et Biophysica Acta - Molecular Basis of Disease Vol.1869 No.5 (2023)
Suggested Citation
Saisomboon S., Kariya R., Boonnate P., Sawanyawisuth K., Cha'on U., Luvira V., Chamgramol Y., Pairojkul C., Seubwai W., Silsirivanit A., Wongkham S., Okada S., Jitrapakdee S., Vaeteewoottacharn K. Diminishing acetyl-CoA carboxylase 1 attenuates CCA migration via AMPK-NF-κB-snail axis. Biochimica et Biophysica Acta - Molecular Basis of Disease Vol.1869 No.5 (2023). doi:10.1016/j.bbadis.2023.166694 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/81592
Title
Diminishing acetyl-CoA carboxylase 1 attenuates CCA migration via AMPK-NF-κB-snail axis
Other Contributor(s)
Abstract
Cholangiocarcinoma (CCA), a cancer of the biliary tract, is a significant health problem in Thailand. Reprogramming of cellular metabolism and upregulation of lipogenic enzymes have been revealed in CCA, but the mechanism is unclear. The current study highlighted the importance of acetyl-CoA carboxylase 1 (ACC1), a rate-limiting enzyme in de novo lipogenesis, on CCA migration. ACC1 expression in human CCA tissues was determined by immunohistochemistry. The results demonstrated that increased ACC1 was related to the shorter survival of CCA patients. Herein, ACC1-deficient cell lines (ACC1-KD) were generated by the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (cas9) system and were used for the comparative study. The ACC1 levels in ACC1-KD were 80–90 % lower than in parental cells. Suppression of ACC1 significantly reduced intracellular malonyl-CoA and neutral lipid contents. Two-fold growth retardation and 60–80 % reduced CCA cell migration and invasion were observed in ACC1-KD cells. The reduced 20–40 % of intracellular ATP levels, AMPK activation, lowered NF-κB p65 nuclear translocation, and snail expression were emphasized. Migration of ACC1-KD cells was restored by supplementation with palmitic acid and malonyl-CoA. Altogether, the importance of rate-limiting enzyme in de novo fatty acid synthesis, ACC1, and AMPK-NF-κB-snail axis on CCA progression was suggested herein. These might be the novel targets for CCA drug design. (ACC1, AMPK, Cholangiocarcinoma, De novo lipogenesis, NF-κB, Palmitic acid)