{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:58:08Z","timestamp":1768568288048,"version":"3.49.0"},"posted":{"date-parts":[[2024,3,13]]},"group-title":"Oncology","reference-count":50,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,3,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Colorectal (CRC) and gastric (GC) cancers remain the top lethal cancers and targeted therapies in this setting are still very limited. Sialyl Lewis X (SLeX), a cancer-associated glycan highly expressed in both CRC and GC, plays a crucial role in cancer cell dissemination and metastasis. Thus, presenting a promising but still underexplored therapeutic target. In this work, we performed a high-throughput screening (HTS) approach to identify potential inhibitors of SLeX expression on cancer cells. Two libraries including a total of 7836 compounds were screened and monensin emerged as a promising SLeX inhibitor. Monensin promoted structural alterations in the secretory pathway, particularly at the Golgi apparatus, impacting protein\n                  <jats:italic>O<\/jats:italic>\n                  -glycosylation and secretion. RNAseq transcriptomic analysis uncovered significant alterations in Gene Ontology (GO) terms associated with protein misfolding, target to the membrane, as well as, epithelial cell-cell adhesion protein.\n                  <jats:italic>In vitro<\/jats:italic>\n                  studies showed that, upon treatment with monensin, SLeX-positive cancer cells showed reduced viability, concomitant with decreased motility and invasive capacities. Using\n                  <jats:italic>in vivo<\/jats:italic>\n                  xenograft models of chick embryo chorioallantoic membrane (CAM) and nude mice, revealed that monensin reduced tumor formation and invasion. Pre-clinical validation using gastric cancer patient-derived organoids (PDOs) and organoid xenotransplants in mice further underscored the clinical potential of monensin in suppressing the growth of SLeX- positive tumors. Overall, our findings set the ground for further evaluation of monensin as a novel therapeutic agent in GC and CRC in the clinical setting.\n                <\/jats:p>","DOI":"10.1101\/2024.03.11.24304048","type":"posted-content","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T13:50:38Z","timestamp":1710337838000},"source":"Crossref","is-referenced-by-count":2,"title":["Monensin as potential drug for treatment of SLeX-positive tumors"],"prefix":"10.64898","author":[{"given":"Ana F.","family":"Costa","sequence":"first","affiliation":[]},{"given":"Emanuel","family":"Senra","sequence":"additional","affiliation":[]},{"given":"Diana","family":"Campos","sequence":"additional","affiliation":[]},{"given":"Isabel","family":"Faria-Ramos","sequence":"additional","affiliation":[]},{"given":"Liliana","family":"Santos-Ferreira","sequence":"additional","affiliation":[]},{"given":"Sofia","family":"Lamas","sequence":"additional","affiliation":[]},{"given":"Joana","family":"Gomes","sequence":"additional","affiliation":[]},{"given":"Filipe","family":"Pinto","sequence":"additional","affiliation":[]},{"given":"Andreia","family":"Teixeira","sequence":"additional","affiliation":[]},{"given":"Rafaela","family":"Abrantes","sequence":"additional","affiliation":[]},{"given":"Henrique O.","family":"Duarte","sequence":"additional","affiliation":[]},{"given":"Mariana","family":"Pacheco","sequence":"additional","affiliation":[]},{"given":"Marta T.","family":"Pinto","sequence":"additional","affiliation":[]},{"given":"Andr\u00e9 F.","family":"Maia","sequence":"additional","affiliation":[]},{"given":"Ant\u00f3nio","family":"Pombinho","sequence":"additional","affiliation":[]},{"given":"Rita","family":"Barros","sequence":"additional","affiliation":[]},{"given":"Ver\u00f3nica","family":"Fernandes","sequence":"additional","affiliation":[]},{"given":"Frederica","family":"Casanova-Gon\u00e7alves","sequence":"additional","affiliation":[]},{"given":"Fabiana","family":"Sousa","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9","family":"Barbosa","sequence":"additional","affiliation":[]},{"given":"Lu\u00edsa","family":"Pereira","sequence":"additional","affiliation":[]},{"given":"F\u00e1tima","family":"Carneiro","sequence":"additional","affiliation":[]},{"given":"Celso A.","family":"Reis","sequence":"additional","affiliation":[]},{"given":"Catarina","family":"Gomes","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2024031501250551000_2024.03.11.24304048v1.1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djm135"},{"key":"2024031501250551000_2024.03.11.24304048v1.2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"2024031501250551000_2024.03.11.24304048v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3982"},{"key":"2024031501250551000_2024.03.11.24304048v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2019.06.006"},{"key":"2024031501250551000_2024.03.11.24304048v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(98)70529-3"},{"issue":"24","key":"2024031501250551000_2024.03.11.24304048v1.6","doi-asserted-by":"crossref","first-page":"7431","DOI":"10.7150\/thno.33858","article-title":"Carcinoembryonic antigen carrying SLe(X) as a new biomarker of more aggressive gastric carcinomas","volume":"9","year":"2019","journal-title":"Theranostics"},{"key":"2024031501250551000_2024.03.11.24304048v1.7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066737"},{"key":"2024031501250551000_2024.03.11.24304048v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2008.06.002"},{"key":"2024031501250551000_2024.03.11.24304048v1.9","doi-asserted-by":"crossref","unstructured":"Trinchera, M. , A. 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