{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T13:31:37Z","timestamp":1773149497005,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,22]],"date-time":"2024-09-22T00:00:00Z","timestamp":1726963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["IRN59W0003"],"award-info":[{"award-number":["IRN59W0003"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]},{"name":"IRN-Cancer Metabolism and Drug Target (CMD)","award":["IRN59W0003"],"award-info":[{"award-number":["IRN59W0003"]}]},{"name":"Japan Student Services Organization (JASSO)","award":["IRN59W0003"],"award-info":[{"award-number":["IRN59W0003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\/GSK3\u03b2\/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.<\/jats:p>","DOI":"10.3390\/ijms251810170","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T03:36:38Z","timestamp":1727062598000},"page":"10170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Augmented Global Protein Acetylation Diminishes Cell Growth and Migration of Cholangiocarcinoma Cells"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8237-8230","authenticated-orcid":false,"given":"Saowaluk","family":"Saisomboon","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryusho","family":"Kariya","sequence":"additional","affiliation":[{"name":"Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan"},{"name":"Laboratory of Molecular Cellular Biology, School of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4389-334X","authenticated-orcid":false,"given":"Panupong","family":"Mahalapbutr","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Center of Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1185-6691","authenticated-orcid":false,"given":"Tonkla","family":"Insawang","sequence":"additional","affiliation":[{"name":"Research Instrument Center, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanlayanee","family":"Sawanyawisuth","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Center of Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9909-8671","authenticated-orcid":false,"given":"Ubon","family":"Cha\u2019on","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7402-3235","authenticated-orcid":false,"given":"Thanyada","family":"Rungrotmongkol","sequence":"additional","affiliation":[{"name":"Center of Excellence in Structural and Computational Biology, Department of Biochemistry, Faculty of Science, and Program in Bioinformatics and Computational Biology, Graduated School, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9578-3041","authenticated-orcid":false,"given":"Sopit","family":"Wongkham","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan"},{"name":"Center of Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarawut","family":"Jitrapakdee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3124-5206","authenticated-orcid":false,"given":"Seiji","family":"Okada","sequence":"additional","affiliation":[{"name":"Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6557-9680","authenticated-orcid":false,"given":"Kulthida","family":"Vaeteewoottacharn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"},{"name":"Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection and Graduate School Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan"},{"name":"Center of Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41575-020-0310-z","article-title":"Cholangiocarcinoma 2020: The next horizon in mechanisms and management","volume":"17","author":"Banales","year":"2020","journal-title":"Nat. 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