Study Identifies Galectin-3's Role in Gastric Metaplasia Development Through Cathartocytosis
Researchers have identified that galectin-3, a lectin protein, plays a necessary role in facilitating cathartocytosis — a cellular content-expulsion process — that accelerates the development of spasmolytic polypeptide-expressing metaplasia (SPEM), a precancerous stomach condition. The study used a chemically-induced mouse model to show that galectin-3 co-localizes with sulfated mucins in gastric chief cells and selectively promotes vesicle expulsion, which in turn triggers expression of the metaplastic transcription factor Sox9 and drives cell proliferation. These findings matter because they reveal a previously unrecognized mechanism by which galectin-3 promotes the transition from normal gastric tissue to high-risk premalignant metaplasia, while also resolving a longstanding controversy about how galectins are secreted outside of canonical pathways.
A new preprint study on bioRxiv reports that galectin-3, a carbohydrate-binding protein known to be upregulated in high-risk gastrointestinal metaplasias, actively facilitates a process called cathartocytosis — the selective expulsion of vesicle contents from cells — in gastric chief cells following tissue injury. Using a synchronous, chemically-induced murine model of SPEM, the researchers demonstrated that galectin-3 co-localizes specifically with sulfomucins inside zymogenic granules and promotes the expulsion of only those vesicles it occupies, leaving organelles lacking galectin-3 unaffected. When this cellular downscaling process was inhibited, the expression of Sox9, a transcription factor associated with metaplastic reprogramming, was delayed, and cell proliferation was reduced. The study also found that injury induces Lgals3 expression at both the RNA and protein levels in vivo, a pattern distinct from what is observed in cancer cell lines. Importantly, the findings propose cathartocytosis as an unconventional secretory pathway for galectin-3, addressing a long-debated question since galectins lack the signal sequences required for classical secretory routes. Both galectin-3 and sulfated glycotopes are known to be concurrently overexpressed in premalignant conditions such as Barrett's esophagus, type III intestinal metaplasia, and pancreatic intraepithelial neoplasia, suggesting the mechanism identified here may have broader relevance across gastrointestinal cancers.
What's missing
As a preprint, this study has not yet undergone peer review, and its findings should be interpreted with caution. The study relies entirely on a chemically-induced mouse model, and it is unclear whether the same galectin-3-driven cathartocytosis mechanism operates in human gastric tissue or in spontaneous (non-chemically-induced) metaplasia. The authors do not address whether therapeutic inhibition of galectin-3 or cathartocytosis at this stage would be feasible or safe, nor do they clarify the downstream molecular steps linking cathartocytosis to Sox9 activation.
What different sources said
- bioRxivCenter
Galectin-3 is Necessary for Selective Cathartocytosis, which Expedites the Development of Proliferative Gastric SPEM
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