{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:04:05Z","timestamp":1782975845621,"version":"3.54.5"},"reference-count":70,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Medical University","award":["CMU107-ASIA-13"],"award-info":[{"award-number":["CMU107-ASIA-13"]}]},{"name":"China Medical University","award":["DMR-107-037"],"award-info":[{"award-number":["DMR-107-037"]}]},{"name":"China Medical University Hospital","award":["CMU107-ASIA-13"],"award-info":[{"award-number":["CMU107-ASIA-13"]}]},{"name":"China Medical University Hospital","award":["DMR-107-037"],"award-info":[{"award-number":["DMR-107-037"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Colorectal cancer remains a leading malignancy. As the aberrant activation of Wnt\/\u03b2-catenin signaling causes colorectal cancer, Wnt\/\u03b2-catenin signaling inhibitors are potential candidates for colorectal cancer treatment. Our drug screening platform identified ursolic acid (UA), a triterpenoid with various biological activities, as a potential anticancer drug because it inhibits the T-cell factor (TCF)\/\u03b2-catenin-mediated transcriptional activity. Here, we discovered that UA inhibited Wnt signaling by reducing the Wnt reporter activity and Wnt target gene expression, leading to a delay in cell cycle progression and the suppression of cell proliferation. Stepwise epistatic analyses suggested that UA functions on \u03b2-catenin protein stability in Wnt signaling. Further studies revealed that UA reduced \u03b2-catenin protein levels by Western blotting and immunofluorescent staining and induced autophagy by microtubule-associated protein 1 light chain 3 beta (LC3B) punctate staining. The cotreatment with UA and the autophagy inhibitors chloroquine and wortmannin recovered the \u03b2-catenin protein levels. Therefore, UA was confirmed to induce \u03b2-catenin degradation by the autophagy\u2013lysosomal degradation system through inhibition in the phosphatidylinositol 3-kinase (PI3K)\/Ak strain transforming (protein kinase B; AKT)\/mammalian target of rapamycin (mTOR) signaling pathway. Our results not only highlight the potential of UA in Wnt-driven colorectal cancer therapy but also provide a workable Wnt signaling termination approach for the treatment of other Wnt-related diseases.<\/jats:p>","DOI":"10.3390\/ijms26136210","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:28:28Z","timestamp":1751347708000},"page":"6210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Ursolic Acid Suppresses Colorectal Cancer Through Autophagy\u2013Lysosomal Degradation of \u03b2-Catenin"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1196-4118","authenticated-orcid":false,"given":"Chung-Ming","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Ming Chuan University, Taoyuan 33348, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Chih","family":"Chao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Han","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery, China Medical University Hospital, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Jye","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"dev146589","DOI":"10.1242\/dev.146589","article-title":"Wnt signaling in development and tissue homeostasis","volume":"145","author":"Steinhart","year":"2018","journal-title":"Development"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1021\/acs.jafc.3c07536","article-title":"Therapeutic Potential of Natural Compounds from Herbs and Nutraceuticals in Alleviating Neurological Disorders: Targeting the Wnt Signaling Pathway","volume":"72","author":"Li","year":"2024","journal-title":"J. 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