{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:00Z","timestamp":1787028540017,"version":"build-2736575974"},"reference-count":43,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chinese Scholarship Council","award":["201607040063"],"award-info":[{"award-number":["201607040063"]}]},{"name":"European Association for the Study of the Liver, EASL Sheila Sherlock Fellowship","award":["201607040063"],"award-info":[{"award-number":["201607040063"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cholangiocarcinoma (CCA), or bile duct cancer, is the second most common liver malignancy, with an increasing incidence in Western countries. The lack of effective treatments associated with the absence of early symptoms highlights the need to search for new therapeutic targets for CCA. Sulfatides (STs), a type of sulfoglycosphingolipids, have been found in the biliary tract, with increased levels in CCA and other types of cancer. STs are involved in protein trafficking and cell adhesion as part of the lipid rafts of the plasma membrane. We aimed to study the role of STs in CCA by the genetic targeting of GAL3ST1, an enzyme involved in ST synthesis. We used the CRISPR-Cas9 system to generate GAL3ST1-deficient TFK1 cells. GAL3ST1 KO cells showed lower proliferation and clonogenic activity and reduced glycolytic activity compared to TFK1 cells. Polarized TFK1 GAL3ST1 KO cells displayed increased transepithelial resistance and reduced permeability compared to TFK1 wt cells. The loss of GAL3ST1 showed a negative effect on growth in 30 out of 34 biliary tract cancer cell lines from the DepMap database. GAL3ST1 deficiency partially restored epithelial identity and barrier function and reduced proliferative activity in CCA cells. Sulfatide synthesis may provide a novel therapeutic target for CCA.<\/jats:p>","DOI":"10.3390\/ijms25137279","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:58:42Z","timestamp":1719925122000},"page":"7279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["GAL3ST1 Deficiency Reduces Epithelial\u2013Mesenchymal Transition and Tumorigenic Capacity in a Cholangiocarcinoma Cell Line"],"prefix":"10.3390","volume":"25","author":[{"given":"Lin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Surgery, School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Elizalde","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology-Hepatology, Department of Internal Medicine, Maastricht University, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8887-4137","authenticated-orcid":false,"given":"Ludwig J.","family":"Dubois","sequence":"additional","affiliation":[{"name":"The M-Lab, Department of Precision Medicine, Maastricht University, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1670-7487","authenticated-orcid":false,"given":"Anjali A.","family":"Roeth","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 MD Maastricht, The Netherlands"},{"name":"Department of General, Visceral and Transplant Surgery, University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf P.","family":"Neumann","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 MD Maastricht, The Netherlands"},{"name":"Department of General, Visceral and Transplant Surgery, University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5202-9345","authenticated-orcid":false,"given":"Steven W. M.","family":"Olde Damink","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 MD Maastricht, The Netherlands"},{"name":"Department of General, Visceral and Transplant Surgery, University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1597-572X","authenticated-orcid":false,"given":"Frank G.","family":"Schaap","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 MD Maastricht, The Netherlands"},{"name":"Department of General, Visceral and Transplant Surgery, University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5943-0310","authenticated-orcid":false,"given":"Gloria","family":"Alvarez-Sola","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.critrevonc.2016.11.012","article-title":"Cholangiocarcinoma","volume":"116","author":"Squadroni","year":"2017","journal-title":"Crit. 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