{"doi":"10.3390/cells11203294","title":"USP7 Induces Chemoresistance in Triple-Negative Breast Cancer via Deubiquitination and Stabilization of ABCB1","abstract":"<jats:p>Triple-negative breast cancer (TNBC) accounts for 15–20% of all breast cancer. TNBC does not express the estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. Cytotoxic chemotherapy and surgery are the current therapeutic strategies for TNBC patients, but the chemoresistance of TNBC limits the efficiency of this strategy and shortens the lifespan of patients. The exploration of targeted therapy is ongoing in TNBC research. The aim of the present study was to identify the mechanism underlying acquired resistance in TNBC through the exploration of the relationship between the expression of USP7 and of ABCB1. We found that ubiquitin specific protease 7 (USP7) is a potential therapeutic target for overcoming the chemoresistance of TNBC. USP7 overexpression increased the chemoresistance of TNBC, while the knockdown of USP7 effectively increased the chemosensitivity of chemoresistant TNBC. A USP7 inhibitor effectively induced apoptosis and suppressed metastasis in chemoresistant TNBC. We further clarified that USP7 is a specific deubiquitinating enzyme for ABCB1 that plays an essential role in drug resistance. USP7 directly interacted with ABCB1 and regulated its stability. We concluded that USP7 promotes the chemoresistance of TNBC by stabilizing the ABCB1 protein.</jats:p>","journal":"Cells","year":2022,"id":622610,"datarank":0.5676284450877392,"base_score":3.784189633918261,"endowment":3.784189633918261,"self_citation_contribution":0.5676284450877392,"citation_network_contribution":0.0,"self_endowment_contribution":0.5676284450877392,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":12,"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":979034,"name":"Joseph Lin","orcid":"0000-0003-0623-816X","position":1,"is_corresponding":false},{"id":1608746,"name":"Yi-En Liu","orcid":null,"position":2,"is_corresponding":false},{"id":1608747,"name":"Yun-Cen Chen","orcid":null,"position":3,"is_corresponding":false},{"id":1608748,"name":"Shiang-Ting Liu","orcid":null,"position":4,"is_corresponding":false},{"id":160593,"name":"Kai-Wen Hsu","orcid":null,"position":5,"is_corresponding":false},{"id":1608749,"name":"Dar-Ren Chen","orcid":"0000-0002-0897-4374","position":6,"is_corresponding":false},{"id":1608750,"name":"Han-Tsang Wu","orcid":"0000-0003-0562-0375","position":7,"is_corresponding":false},{"id":1359523,"name":"Yueh-Te Lin","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"USP7 Induces Chemoresistance in Triple-Negative Breast Cancer via Deubiquitination and Stabilization of ABCB1","abstract":"<jats:p>Triple-negative breast cancer (TNBC) accounts for 15–20% of all breast cancer. TNBC does not express the estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. Cytotoxic chemotherapy and surgery are the current therapeutic strategies for TNBC patients, but the chemoresistance of TNBC limits the efficiency of this strategy and shortens the lifespan of patients. The exploration of targeted therapy is ongoing in TNBC research. The aim of the present study was to identify the mechanism underlying acquired resistance in TNBC through the exploration of the relationship between the expression of USP7 and of ABCB1. We found that ubiquitin specific protease 7 (USP7) is a potential therapeutic target for overcoming the chemoresistance of TNBC. USP7 overexpression increased the chemoresistance of TNBC, while the knockdown of USP7 effectively increased the chemosensitivity of chemoresistant TNBC. A USP7 inhibitor effectively induced apoptosis and suppressed metastasis in chemoresistant TNBC. We further clarified that USP7 is a specific deubiquitinating enzyme for ABCB1 that plays an essential role in drug resistance. USP7 directly interacted with ABCB1 and regulated its stability. We concluded that USP7 promotes the chemoresistance of TNBC by stabilizing the ABCB1 protein.</jats:p>","is_dataset_classified":null,"base_score":3.784189633918261,"endowment":3.784189633918261,"datacite_reuse_total":12,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36291159","pmcid":"PMC9600340","openalex_id":"https://openalex.org/W4306836424","authors":[],"funders":[{"funder_name":"Ministry of Science and Technology Summit","grant_id":"MOST 110-2314-B-371-007-MY3","title":null},{"funder_name":"Ministry of Science and Technology Summit","grant_id":"111-CCH-IRP-037","title":null},{"funder_name":"Ministry of Science and Technology Summit","grant_id":"MOST 110-2314-B-182A-011","title":null},{"funder_name":"Ministry of Science and Technology Summit","grant_id":"CMU110-MF-10","title":null},{"funder_name":"Featured Areas Research Center Program within the framework of the Higher Education Sprout Project","grant_id":"","title":null}],"total_grants":5,"fwci":2.9001,"citation_percentile":0.92556996,"influential_citations":0,"citation_trend":[{"year":2022,"count":1},{"year":2023,"count":5},{"year":2024,"count":24},{"year":2025,"count":7},{"year":2026,"count":6}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2073-4409/11/20/3294/pdf?version=1666598198","host_type":"journal"},{"url":"https://www.mdpi.com/2073-4409/11/20/3294/pdf?version=1666598198","host_type":"publisher"},{"url":"https://www.mdpi.com/2073-4409/11/20/3294/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/cells11203294","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36291159","host_type":"repository"},{"url":"https://doaj.org/article/93b89a606a8247e0a89870738014bd5c","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/cells11203294","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9600340","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9600340","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9600340?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Ubiquitin and proteasome pathways","Cancer-related Molecular Pathways","Histone Deacetylase Inhibitors Research","Humans","Triple Negative Breast Neoplasms","Ubiquitin-Specific Peptidase 7","Drug Resistance, Neoplasm","Receptors, Progesterone","Cell Line, Tumor","ATP Binding Cassette Transporter, Subfamily B, Member 1","Estrogens","ATP Binding Cassette Transporter, Subfamily B"],"mesh_terms":["Ubiquitin-Specific Peptidase 7","Estrogens","Humans","Receptors, Progesterone","ATP Binding Cassette Transporter, Subfamily B","Drug Resistance, Neoplasm","ATP Binding Cassette Transporter, Subfamily B, Member 1","Cell Line, Tumor","Triple Negative Breast Neoplasms"],"keywords":["Triple-negative breast cancer","Cancer research","Deubiquitinating enzyme","Breast cancer","Estrogen receptor","Gene knockdown","Cancer","Metastasis","Progesterone receptor","Medicine","Apoptosis","Drug resistance","Biology","Internal medicine","Ubiquitin","Chemoresistance","Ubiquitin Specific Protease 7","Atp-binding Cassette B1"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.26716021.v1","title":"Additional file 4 of The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.26716024","title":"Additional file 5 of The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.26716024.v1","title":"Additional file 5 of The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.26716021","title":"Additional file 4 of The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.26716027.v1","title":"Additional file 6 of The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.26716027","title":"Additional file 6 of The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.25749972","title":"Additional file 1 of The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.25750164.v1","title":"Additional file 2 of The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.25749972.v1","title":"Additional file 1 of The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.25750164","title":"Additional file 2 of The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.26716018.v1","title":"Additional file 3 of The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis","publisher":"figshare","resource_type":"Image"},{"doi":"10.6084/m9.figshare.26716018","title":"Additional file 3 of The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis","publisher":"figshare","resource_type":"Image"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T20:17:57.182581Z","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":[]}