{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T05:53:10Z","timestamp":1776750790300,"version":"3.51.2"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The molecular heterogeneity of colorectal cancer (CRC) profoundly shapes clinical outcomes and treatment response, underscoring the need to elucidate the underlying mechanisms to refine diagnosis and therapy. Although LGALS3, which encodes Galectin-3 (Gal-3), has been implicated in tumor biology, its precise role and regulatory mechanism in CRC remain incompletely understood. This study aimed to define the clinical relevance and mechanistic function of the Gal-3-related signaling axis in CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated TCGA and single-cell RNA sequencing data to evaluate the clinical significance of LGALS3 in CRC. Molecular investigations, including co-immunoprecipitation and ubiquitination assays, were performed to examine how Gal-3 regulated FBXL5 and YAP1. Functional effects were further assessed using cell proliferation assays and xenograft mouse models to investigate the biological role of the Gal-3-FBXL5-YAP1 axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Gal-3 positively correlated with FBXL5 and bound FBXL5 to enhance its expression. Patients with high LGALS3 and FBXL5 expression exhibited better survival. Mechanistically, FBXL5 promoted YAP1 protein degradation through the ubiquitin pathway without altering YAP1 transcript levels, suggesting a post-transcriptional regulatory mechanism. Gal-3 increased FBXL5 abundance and promoted YAP1 degradation, thereby supporting the existence of a Gal-3-FBXL5-YAP1 regulatory axis. In vivo, LGALS3 knockdown markedly increased tumor volume, whereas FBXL5 overexpression reduced tumor growth. YAP1 protein expression patterns were consistent with these findings. Cell proliferation assays and xenograft experiments further supported an antitumor effect of this signaling axis in CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study suggests that the Gal-3-FBXL5-YAP1 axis plays an important role in restraining CRC progression, expands the mechanistic understanding of Gal-3-associated tumor suppression, and supports Gal-3 as a potential therapeutic target in CRC. Nevertheless, additional validation using TEAD reporter assays and YAP1 rescue or mutant analyses will be required to further strengthen the causal framework of this axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1769656","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T05:34:23Z","timestamp":1776749663000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Galectin-3 promotes FBXL5-dependent ubiquitination and degradation of YAP1 to constrain colorectal cancer growth"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiang","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Tumor Surgery, Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsz Kin","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tumor Surgery, Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Tumor Surgery, Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiliang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department 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