{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T11:00:15Z","timestamp":1787828415805,"version":"build-2784847793"},"reference-count":64,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Traditional Chinese and Western Medicine Collaborative Guidance Project of Integrated Hospital from Shanghai Municipal Health Commission\/Shanghai Municipal Administration of Traditional Chinese Medicine","award":["ZXXT-202303"],"award-info":[{"award-number":["ZXXT-202303"]}]},{"name":"Traditional Chinese and Western Medicine Collaborative Guidance Project of Integrated Hospital from Shanghai Municipal Health Commission\/Shanghai Municipal Administration of Traditional Chinese Medicine","award":["YDZX20223100001004"],"award-info":[{"award-number":["YDZX20223100001004"]}]},{"name":"Traditional Chinese and Western Medicine Collaborative Guidance Project of Integrated Hospital from Shanghai Municipal Health Commission\/Shanghai Municipal Administration of Traditional Chinese Medicine","award":["2024YFC3506700"],"award-info":[{"award-number":["2024YFC3506700"]}]},{"name":"Traditional Chinese and Western Medicine Collaborative Guidance Project of Integrated Hospital from Shanghai Municipal Health Commission\/Shanghai Municipal Administration of Traditional Chinese Medicine","award":["2024YFC3506704"],"award-info":[{"award-number":["2024YFC3506704"]}]},{"name":"Shanghai Science and Technology Development Fund from Central Leading Local Government","award":["ZXXT-202303"],"award-info":[{"award-number":["ZXXT-202303"]}]},{"name":"Shanghai Science and Technology Development Fund from Central Leading Local Government","award":["YDZX20223100001004"],"award-info":[{"award-number":["YDZX20223100001004"]}]},{"name":"Shanghai Science and Technology Development Fund from Central Leading Local Government","award":["2024YFC3506700"],"award-info":[{"award-number":["2024YFC3506700"]}]},{"name":"Shanghai Science and Technology Development Fund from Central Leading Local Government","award":["2024YFC3506704"],"award-info":[{"award-number":["2024YFC3506704"]}]},{"name":"National Key R&amp;D Program of China","award":["ZXXT-202303"],"award-info":[{"award-number":["ZXXT-202303"]}]},{"name":"National Key R&amp;D Program of China","award":["YDZX20223100001004"],"award-info":[{"award-number":["YDZX20223100001004"]}]},{"name":"National Key R&amp;D Program of China","award":["2024YFC3506700"],"award-info":[{"award-number":["2024YFC3506700"]}]},{"name":"National Key R&amp;D Program of China","award":["2024YFC3506704"],"award-info":[{"award-number":["2024YFC3506704"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cervical cancer ranks as the fourth most prevalent cancer and cause of cancer-related mortality among women globally. It exhibits a recurrence\/metastasis rate of approximately 30% and a dismal 5-year survival of only 17% in metastatic cases. Despite significant advancements in surgical techniques, chemoradiotherapy, and targeted therapies, effective treatment options for metastatic cervical cancer remain limited. This study explored Polyphyllin I (PPI), which is a monomeric compound derived from the Rhizoma of Paris Polyphyllin, as a potential inhibitor of cervical cancer metastasis. Mechanistically, PPI directly interacted with \u03b2-catenin at the Ser552 site, inhibiting its phosphorylation and subsequent nuclear translocation, thereby suppressing TCF\/LEF transcriptional activity and downstream EMT transcription factors (ZEB1, Slug, Snail, and Twist). Notably, PPI promoted \u03b2-catenin degradation via the autophagy\u2013lysosomal pathway, as confirmed by CHX chase assays and the detection of the p62 and LC3 proteins, without altering the mRNA levels of \u03b2-catenin. In vitro experiments demonstrated that PPI effectively suppressed the migration and invasion of HO-8910PM cells by reversing the process of EMT. Additionally, PPI effectively inhibited TCF\/LEF signaling, leading to a reduction in the transcription levels of EMT-associated transcription factors (EMT-TFs), which was mediated by the TCF\/LEF family downstream of \u03b2-catenin. Furthermore, PPI exhibited inhibitory effects on proliferation, migration, and invasion in both HPV-positive (SiHa) and HPV-negative (C33A) cervical cancer cells. In vivo, PPI significantly suppressed peritoneal metastasis in a luciferase-labeled HO-8910PM xenograft mouse model. These findings reveal the dual role of PPI in blocking \u03b2-catenin signaling and inducing \u03b2-catenin depletion, thereby effectively restraining metastatic progression. This study underscores the potential of PPI as a promising therapeutic candidate for targeting cervical cancer metastasis through autophagy-mediated \u03b2-catenin regulation, offering a novel strategy to address current treatment limitations.<\/jats:p>","DOI":"10.3390\/ijms26104630","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T12:18:06Z","timestamp":1747052286000},"page":"4630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Polyphyllin I Inhibits the Metastasis of Cervical Cancer Through the Regulation of the \u03b2-Catenin Signaling Pathway"],"prefix":"10.3390","volume":"26","author":[{"given":"Yingbin","family":"Chai","sequence":"first","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaopeng","family":"Yu","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiang","family":"Lin","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunying","family":"Luo","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawen","family":"Peng","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiange","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Volkova, L.V., Pashov, A.I., and Omelchuk, N.N. 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