{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T23:58:21Z","timestamp":1781654301795,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Intrahepatic cholangiocarcinoma (iCCA) is a primary liver tumour, characterized by poor prognosis and lack of effective therapy. The cytoskeleton protein Filamin A (FLNA) is involved in cancer progression and metastasis, including primary liver cancer. FLNA is cleaved by calpain, producing a 90\u2009kDa fragment (FLNA<jats:sup>CT<\/jats:sup>) that can translocate to the nucleus and inhibit gene transcription. We herein aim to define the role of FLNA and its cleavage in iCCA carcinogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods &amp; Results<\/jats:title><jats:p>We evaluated the expression and localization of FLNA and FLNA<jats:sup>CT<\/jats:sup> in liver samples from iCCA patients (<jats:italic>n<\/jats:italic>\u2009=\u200982) revealing that FLNA expression was independently correlated with disease\u2010free survival. Primary tumour cells isolated from resected iCCA patients expressed both FLNA and FLNA<jats:sup>CT<\/jats:sup>, and bulk RNA sequencing revealed a significant enrichment of cell proliferation and cell motility pathways in iCCAs with high FLNA expression. Further, we defined the impact of FLNA and FLNA<jats:sup>CT<\/jats:sup> on the proliferation and migration of primary iCCA cells (<jats:italic>n<\/jats:italic>\u2009=\u20093) and HuCCT1 cell line using silencing and Calpeptin, a calpain inhibitor. We observed that FLNA silencing decreased cell proliferation and migration and Calpeptin was able to reduce FLNA<jats:sup>CT<\/jats:sup> expression in both the HuCCT1 and iCCA cells (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05 vs. control). Moreover, Calpeptin 100\u2009\u03bcM decreased HuCCT1 and primary iCCA cell proliferation (<jats:italic>p<\/jats:italic>\u2009&lt;.00001 vs. control) and migration (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05 vs. control).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings demonstrate that FLNA is involved in human iCCA progression and calpeptin strongly decreased FLNA<jats:sup>CT<\/jats:sup> expression, reducing cell proliferation and migration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15800","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T01:18:37Z","timestamp":1701134317000},"page":"518-531","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Filamin A is involved in human intrahepatic cholangiocarcinoma aggressiveness and progression"],"prefix":"10.1111","volume":"44","author":[{"given":"Eleonora","family":"Vitali","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Molecular Endocrinology, IRCCS Humanitas Research Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Franceschini","sequence":"additional","affiliation":[{"name":"Hepatobiliary Immunopathology Laboratory, IRCCS Humanitas Research Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio","family":"Milana","sequence":"additional","affiliation":[{"name":"Division of Hepatobiliary and General Surgery, Department of Surgery, IRCCS Humanitas Research Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Soldani","sequence":"additional","affiliation":[{"name":"Hepatobiliary Immunopathology Laboratory, IRCCS Humanitas Research Hospital  Milan 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Biomedical Sciences Humanitas University  Milan Italy"},{"name":"Endocrinology, Diabetology and Medical Andrology Unit IRCCS Humanitas Research Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Donadon","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Universit\u00e0 del Piemonte Orientale  Novara Italy"},{"name":"Department of General Surgery University Maggiore Hospital  Novara 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