Augmented Global Protein Acetylation Diminishes Cell Growth and Migration of Cholangiocarcinoma Cells
Issued Date
2024-09-01
Resource Type
ISSN
16616596
eISSN
14220067
Scopus ID
2-s2.0-85205223689
Pubmed ID
39337655
Journal Title
International Journal of Molecular Sciences
Volume
25
Issue
18
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Molecular Sciences Vol.25 No.18 (2024)
Suggested Citation
Saisomboon S., Kariya R., Mahalapbutr P., Insawang T., Sawanyawisuth K., Cha’on U., Rungrotmongkol T., Wongkham S., Jitrapakdee S., Okada S., Vaeteewoottacharn K. Augmented Global Protein Acetylation Diminishes Cell Growth and Migration of Cholangiocarcinoma Cells. International Journal of Molecular Sciences Vol.25 No.18 (2024). doi:10.3390/ijms251810170 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/101516
Title
Augmented Global Protein Acetylation Diminishes Cell Growth and Migration of Cholangiocarcinoma Cells
Corresponding Author(s)
Other Contributor(s)
Abstract
We have previously shown that the overexpression of acetyl-CoA carboxylase 1 (ACC1) was associated with the poor prognosis of cholangiocarcinoma (CCA) patients, and suppression of its expression in CCA cell lines deteriorated cell growth. The present study explored the mechanism by which ACC1 inhibition affects global protein acetylation, using genetic knockdown and pharmacological inhibition with an ACC1 inhibitor ND-646 as models. Both ACC1 knockdown and ACC1-inhibitor-treated cells displayed the hyperacetylation of proteins, accompanied by impaired growth and migration. The immunoprecipitation of hyperacetylated proteins using the anti-acetylated lysine antibody, followed by tandem mass spectrometry, identified three potential verification candidates, namely POTE ankyrin domain family member E, peroxisomal biogenesis factor 1, and heat shock protein 90 beta (HSP90B). HSP90 acetylation was the candidate selected for the verification of protein acetylation. To establish the effects of protein hyperacetylation, treatment with suberoylanilide hydroxamic acid (SAHA), a lysine deacetylase inhibitor, was conducted, and this served as an independent model. Decreased tumor growth but increased acetylated protein levels were observed in ACC1-KD xenograft tumors. Hyperacetylated-alleviated cell growth and migration were consistently observed in the SAHA-treated models. The molecular linkage between protein hyperacetylation and the AKT/GSK3β/Snail pathway was demonstrated. This study highlighted the importance of protein acetylation in CCA progression, suggesting that ACC1 and KDAC are potential targets for CCA treatment.