{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:32:18Z","timestamp":1786977138464,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"content-version":"vor","delay-in-days":36,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012245","name":"Science and Technology Planning Project of Guangdong Province","doi-asserted-by":"publisher","award":["2010B301600213"],"award-info":[{"award-number":["2010B301600213"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003785","name":"Guangdong Medical Research Foundation","doi-asserted-by":"publisher","award":["A2022446"],"award-info":[{"award-number":["A2022446"]}],"id":[{"id":"10.13039\/501100003785","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tumor metastasis and recurrence are major causes of mortality in patients with hepatocellular carcinoma (HCC) that is still lack of effective therapeutic targets and drugs. Previous reports implied that ras homolog family member C (RhoC) plays a toxic role on metastasis and proliferation of cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this research, the correlation between RhoC and metastasis ability was confirmed by in\u00a0vitro experiments and TCGA database. We explored whether quercetin could inhibit cell migration or invasion by transwell assay. Real\u2010time PCR, overexpression and ubiquitination assay, etc. were applied in mechanism study. Primary HCC cells and animal models including patient\u2010derived xenografts (PDXs) were employed to evaluate the anti\u2010metastasis effects of quercetin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Clinical relevance and in vitro experiments further confirmed the level of RhoC was positively correlated with invasion and metastasis ability of HCC. Then we uncovered that quercetin could attenuate invasion and metastasis of HCC by downregulating RhoC's level in vitro, in vivo and PDXs. Furthermore, mechanistic investigations displayed quercetin hindered the E3 ligase expression of SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) leading to enhancement of RhoC's ubiquitination and proteasomal degradation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our research has revealed the novel mechanisms quercetin regulates degradation of RhoC level by targeting SMURF2 and identified quercetin may be a potential compound for HCC therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.7082","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T10:59:50Z","timestamp":1709895590000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Quercetin\u2010induced degradation of\n                    <scp>RhoC<\/scp>\n                    suppresses hepatocellular carcinoma invasion and metastasis"],"prefix":"10.1002","volume":"13","author":[{"given":"Chunlong","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery, The first affiliated hospital Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The first affiliated hospital Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deli","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The first affiliated hospital Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8389-1467","authenticated-orcid":false,"given":"Xiao","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University  Guangzhou Guangdong 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