Quercetin‐induced degradation of RhoC suppresses hepatocellular carcinoma invasion and metastasis
Abstract Background 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 proli...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.7082 |
| _version_ | 1797265478031245312 |
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| author | Chunlong Huang Weihua Lai Shuai Mao Deli Song Jihong Zhang Xiao Xiao |
| author_facet | Chunlong Huang Weihua Lai Shuai Mao Deli Song Jihong Zhang Xiao Xiao |
| author_sort | Chunlong Huang |
| collection | DOAJ |
| description | Abstract Background 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. Methods In this research, the correlation between RhoC and metastasis ability was confirmed by in vitro experiments and TCGA database. We explored whether quercetin could inhibit cell migration or invasion by transwell assay. Real‐time PCR, overexpression and ubiquitination assay, etc. were applied in mechanism study. Primary HCC cells and animal models including patient‐derived xenografts (PDXs) were employed to evaluate the anti‐metastasis effects of quercetin. Results 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. Conclusions 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. |
| first_indexed | 2024-04-25T00:45:26Z |
| format | Article |
| id | doaj.art-b4d47d72596a49b5bda156c0e0bd0312 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-25T00:45:26Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-b4d47d72596a49b5bda156c0e0bd03122024-03-12T04:52:34ZengWileyCancer Medicine2045-76342024-02-01134n/an/a10.1002/cam4.7082Quercetin‐induced degradation of RhoC suppresses hepatocellular carcinoma invasion and metastasisChunlong Huang0Weihua Lai1Shuai Mao2Deli Song3Jihong Zhang4Xiao Xiao5Department of Hepatobiliary Surgery, The first affiliated hospital Sun Yat‐Sen University Guangzhou Guangdong ChinaDepartment of Pharmacy, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou Guangdong ChinaDepartment of Hepatobiliary Surgery, The first affiliated hospital Sun Yat‐Sen University Guangzhou Guangdong ChinaDepartment of Pharmacology, Zhongshan School of Medicine Sun Yat‐sen University Guangzhou ChinaDepartment of Hepatobiliary Surgery, The first affiliated hospital Sun Yat‐Sen University Guangzhou Guangdong ChinaDepartment of Pharmacy, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou Guangdong ChinaAbstract Background 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. Methods In this research, the correlation between RhoC and metastasis ability was confirmed by in vitro experiments and TCGA database. We explored whether quercetin could inhibit cell migration or invasion by transwell assay. Real‐time PCR, overexpression and ubiquitination assay, etc. were applied in mechanism study. Primary HCC cells and animal models including patient‐derived xenografts (PDXs) were employed to evaluate the anti‐metastasis effects of quercetin. Results 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. Conclusions 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.https://doi.org/10.1002/cam4.7082hepatocellular carcinomametastasisproteasomal degradationquercetinRhoC |
| spellingShingle | Chunlong Huang Weihua Lai Shuai Mao Deli Song Jihong Zhang Xiao Xiao Quercetin‐induced degradation of RhoC suppresses hepatocellular carcinoma invasion and metastasis Cancer Medicine hepatocellular carcinoma metastasis proteasomal degradation quercetin RhoC |
| title | Quercetin‐induced degradation of RhoC suppresses hepatocellular carcinoma invasion and metastasis |
| title_full | Quercetin‐induced degradation of RhoC suppresses hepatocellular carcinoma invasion and metastasis |
| title_fullStr | Quercetin‐induced degradation of RhoC suppresses hepatocellular carcinoma invasion and metastasis |
| title_full_unstemmed | Quercetin‐induced degradation of RhoC suppresses hepatocellular carcinoma invasion and metastasis |
| title_short | Quercetin‐induced degradation of RhoC suppresses hepatocellular carcinoma invasion and metastasis |
| title_sort | quercetin induced degradation of rhoc suppresses hepatocellular carcinoma invasion and metastasis |
| topic | hepatocellular carcinoma metastasis proteasomal degradation quercetin RhoC |
| url | https://doi.org/10.1002/cam4.7082 |
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