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Galectin-3 is a lectin that preferentially associates with galactose modified by a 3\u2019-O-sulfate relative to its unmodified counterparts and is upregulated as the tissue transitions to high-risk metaplasia, dysplasia, and cancer. Since both galectin-3 and sulfated glycotopes are aberrantly and concurrently overexpressed in high-risk premalignant and malignant tissue transformations, we sought to investigate the role of galectin-3 in the metaplastic reaction. We found that injury induces the expression of\n                  <jats:italic>Lgals3<\/jats:italic>\n                  at the RNA and protein levels. Unlike cancer cell lines, we show that\n                  <jats:italic>in vivo<\/jats:italic>\n                  galectin-3 colocalized with sulfomucins in zymogenic granules of the gastric chief cell. Utilizing a synchronous, chemically-induced murine model that produces spasmolytic polypeptide expressing metaplasia, we found that galectin-3 facilitates cathartocytosis of the vesicles it resides in, but not organelles lacking LGALS3. Inhibition of cellular downscaling resulted in delayed expression of the metaplastic transcription factor Sox9 as well as proliferation. Here, we present a new role for galectin-3 in promoting the transition from normal, homeostatic tissue to metaplasia and our data suggest that cathartocytosis represents an unconventional secretory pathway for galectin-3, which has been a matter of controversy as galectins are not secreted via canonical pathways.\n                <\/jats:p>","DOI":"10.64898\/2026.06.07.729580","type":"posted-content","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T10:00:19Z","timestamp":1781172019000},"source":"Crossref","is-referenced-by-count":0,"title":["Galectin-3 is Necessary for Selective Cathartocytosis, which Expedites the Development of Proliferative Gastric SPEM"],"prefix":"10.64898","author":[{"given":"Xiaobo","family":"Lin","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Washington University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Washington University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Nicolazzi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Washington University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Pan","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Washington University School of Medicine"},{"name":"Department of Public Health Sciences, The Johns Hopskins University, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Hua","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Washington University School of Medicine"},{"name":"Department of Psychiatry, Washington University School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3992-9613","authenticated-orcid":false,"given":"Jeffrey W.","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Washington University School of Medicine"},{"name":"Program of Molecular and Cell Biology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA"},{"name":"Program of Biochemistry, Biophysics, and Structural Biology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA"},{"name":"Program of Developmental, Regenerative, and Stem Cell Biology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026061512201619000_2026.06.07.729580v1.1","doi-asserted-by":"crossref","first-page":"1089028","DOI":"10.3389\/fcell.2023.1089028","article-title":"3\u2019-sulfated Lewis(A\/C): An oncofetal epitope associated with metaplastic and oncogenic plasticity of the gastrointestinal foregut","volume":"11","year":"2023","journal-title":"Front Cell Dev Biol"},{"key":"2026061512201619000_2026.06.07.729580v1.2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910030506"},{"key":"2026061512201619000_2026.06.07.729580v1.3","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-196902000-00016"},{"key":"2026061512201619000_2026.06.07.729580v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800016"},{"key":"2026061512201619000_2026.06.07.729580v1.5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1980.tb02921.x"},{"key":"2026061512201619000_2026.06.07.729580v1.6","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1365-2559.1979.tb02996.x","article-title":"A variant of intestinal metaplasia associated with gastric carcinoma: a histochemical study","volume":"3","year":"1979","journal-title":"Histopathology"},{"key":"2026061512201619000_2026.06.07.729580v1.7","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.12.004"},{"key":"2026061512201619000_2026.06.07.729580v1.8","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199610000-00001"},{"key":"2026061512201619000_2026.06.07.729580v1.9","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.12.002"},{"key":"2026061512201619000_2026.06.07.729580v1.10","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.12.001"},{"key":"2026061512201619000_2026.06.07.729580v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(86)80082-X"},{"key":"2026061512201619000_2026.06.07.729580v1.12","doi-asserted-by":"crossref","unstructured":"Das KK , Brown JW , Fernandez Del-Castillo C , Huynh T , Mills JC , Matsuda Y , Das KM , and Mino-Kenudson M. mAb Das-1 Identifies Pancreatic Ductal Adenocarcinoma and High-grade Pancreatic Intraepithelial Neoplasia with High Accuracy. 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