{"doi":"10.1093/carcin/bgad021","title":"SIAH1/CTR9 axis promotes the epithelial–mesenchymal transition of hepatocellular carcinoma","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>SIAH1 has been reported to participate in several human cancers, including hepatocellular carcinoma (HCC). However, the effect of SIAH1 on the epithelial–mesenchymal transition (EMT) has not been reported in HCC cells. Here, we discovered the inhibitory effect of SIAH1 on HCC cell migration and invasion, which was related with regulating EMT. Molecularly, a yeast two-hybrid experiment indicated that Cln Three Requiring 9 (CTR9) was a potential interacting protein of SIAH1, which was further verified by co-immunoprecipitation assays. Furthermore, SIAH1 inhibited the EMT of HCC cells through negatively regulating CTR9. Importantly, CTR9 was ubiquitinated and degraded by SIAH1 via the proteasome pathway in HCC cells. Additionally, it was showed that SIAH1 mainly mediated the K48-linked polyubiquitination on CTR9. Finally, the protein level of CTR9 was found to be inversely correlated with SIAH1 in human HCC tissues. Summed up all together, these findings reveal that SIAH1/CTR9 axis promotes the EMT of HCC cells and is a promising therapeutic target for HCC therapy.</jats:p>","journal":"Carcinogenesis","year":2023,"id":646426,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1683717,"name":"Pengchao Luo","orcid":null,"position":1,"is_corresponding":false},{"id":1683718,"name":"Kuan Cao","orcid":null,"position":2,"is_corresponding":false},{"id":1683719,"name":"Qinghe Hu","orcid":null,"position":3,"is_corresponding":false},{"id":443147,"name":"Bin Hu","orcid":"0000-0002-3775-387X","position":4,"is_corresponding":false},{"id":1683720,"name":"Licheng Cui","orcid":null,"position":5,"is_corresponding":false},{"id":397409,"name":"Xiaotian Wang","orcid":"0000-0002-5296-8203","position":6,"is_corresponding":false},{"id":687603,"name":"Hengliang Shi","orcid":"0000-0002-9649-1910","position":7,"is_corresponding":false},{"id":1238484,"name":"Bin Zhang","orcid":"0000-0003-2606-5825","position":8,"is_corresponding":false},{"id":1683724,"name":"Renhao Wang","orcid":null,"position":9,"is_corresponding":false},{"id":443821,"name":"Zhiyi Liu","orcid":"0000-0002-8122-8474","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"SIAH1/CTR9 axis promotes the epithelial–mesenchymal transition of hepatocellular carcinoma","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>SIAH1 has been reported to participate in several human cancers, including hepatocellular carcinoma (HCC). However, the effect of SIAH1 on the epithelial–mesenchymal transition (EMT) has not been reported in HCC cells. Here, we discovered the inhibitory effect of SIAH1 on HCC cell migration and invasion, which was related with regulating EMT. Molecularly, a yeast two-hybrid experiment indicated that Cln Three Requiring 9 (CTR9) was a potential interacting protein of SIAH1, which was further verified by co-immunoprecipitation assays. Furthermore, SIAH1 inhibited the EMT of HCC cells through negatively regulating CTR9. Importantly, CTR9 was ubiquitinated and degraded by SIAH1 via the proteasome pathway in HCC cells. Additionally, it was showed that SIAH1 mainly mediated the K48-linked polyubiquitination on CTR9. Finally, the protein level of CTR9 was found to be inversely correlated with SIAH1 in human HCC tissues. Summed up all together, these findings reveal that SIAH1/CTR9 axis promotes the EMT of HCC cells and is a promising therapeutic target for HCC therapy.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37038329","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"81874081","title":null},{"funder_name":"Jiangsu Provincial Commission of Health and Family Planning","grant_id":"M2020082","title":null},{"funder_name":"Xuzhou Institute of Technology","grant_id":"KC20091","title":null},{"funder_name":"Xuzhou Institute of Technology","grant_id":"KC20128","title":null},{"funder_name":"National Natural Science Foundation Cultivation Project of Xuzhou Medical University Affiliated Hospital","grant_id":"2020Z001","title":null},{"funder_name":"National Natural Science Foundation Cultivation Project of Xuzhou Medical University Affiliated Hospital","grant_id":"2020Z006","title":null},{"funder_name":"Outstanding Talents Fund project of Xuzhou Medical University","grant_id":"XYFY2021006","title":null},{"funder_name":"Jiangsu Postgraduate Research Innovation Program","grant_id":"SJCX21_1151","title":null},{"funder_name":"Jiangsu Postgraduate Research Innovation Program","grant_id":"KYCX22_2892","title":null},{"funder_name":"Jiangsu Postgraduate Research Innovation Program","grant_id":"KYCX22_2907","title":null}],"total_grants":10,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":null,"license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://academic.oup.com/carcin/advance-article-pdf/doi/10.1093/carcin/bgad021/50489705/bgad021.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/carcin/article-pdf/44/4/304/50696252/bgad021.pdf","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Cell Line, Tumor","Humans","Carcinoma, Hepatocellular","Liver Neoplasms","Phosphoproteins","Transcription Factors","Cell Proliferation","Cell Movement","Gene Expression Regulation, Neoplastic","Epithelial-Mesenchymal Transition"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-09T13:11:42.826369Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}