{"doi":"10.7150/thno.44567","title":"TGF-β causes Docetaxel resistance in Prostate Cancer via the induction of Bcl-2 by acetylated KLF5 and Protein Stabilization","abstract":"Prostate cancer is the second leading cause of cancer-related death in the United States. As a first line treatment for hormone-refractory prostate cancer, docetaxel (DTX) treatment leads to suboptimal effect since almost all patients eventually develop DTX resistance. In this study, we investigated whether and how TGF- affects DTX resistance of prostate cancer. Methods: Cytotoxicity of DTX in DU 145 and PC-3 cells was measured by CCK-8 and Matrigel colony formation assays. Resistance to DTX in DU 145 cells was examined in a xenograft tumorigenesis model. A luciferase reporter system was used to determine transcriptional activities. Gene expression was analyzed by RT-qPCR and Western blotting. Results: We found that KLF5 is indispensable in TGF--induced DTX resistance. Moreover, KLF5 acetylation at lysine 369 mediates DTX resistance in vitro and in vivo. We showed that the TGF-/acetylated KLF5 signaling axis activates Bcl-2 expression transcriptionally. Furthermore, DTX-induced Bcl-2 degradation depends on a proteasome pathway, and TGF- inhibits DTX-induced Bcl-2 ubiquitination. Conclusion: Our study demonstrated that the TGF--acetylated KLF5-Bcl-2 signaling axis mediates DTX resistance in prostate cancer and blockade of this pathway could provide clinical insights into chemoresistance of prostate cancer.","journal":"Theranostics","year":2020,"id":59825,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":65,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9503,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":315128,"name":"Baotong Zhang","orcid":"0000-0002-6586-4016","position":1,"is_corresponding":false},{"id":128647,"name":"Lingwei Xiang","orcid":null,"position":2,"is_corresponding":false},{"id":315129,"name":"Siyuan Xia","orcid":"0000-0001-6756-3519","position":3,"is_corresponding":false},{"id":315130,"name":"Ömer Küçük","orcid":"0000-0002-4755-0507","position":4,"is_corresponding":false},{"id":315131,"name":"Xingming Deng","orcid":"0000-0003-0319-1511","position":5,"is_corresponding":false},{"id":28928,"name":"Lawrence Boise","orcid":"0000-0001-9436-8815","position":6,"is_corresponding":false},{"id":315132,"name":"Jin‐Tang Dong","orcid":"0000-0003-2349-5782","position":7,"is_corresponding":false},{"id":315127,"name":"Yixiang Li","orcid":"0000-0002-0231-7453","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-18T21:08:26.834549Z","pmid":"32685011","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":[]}