{"doi":"10.3390/cancers15215263","title":"Targeting Translation and the Cell Cycle Inversely Affects CTC Metabolism but Not Metastasis","abstract":"Melanoma brain metastasis (MBM) is significantly associated with poor prognosis and is diagnosed in 80% of patients at autopsy. Circulating tumor cells (CTCs) are \"seeds\" of metastasis and the smallest functional units of cancer. Our multilevel approach has previously identified a CTC RPL/RPS gene signature directly linked to MBM onset. We hypothesized that targeting ribogenesis prevents MBM/metastasis in CTC-derived xenografts. We treated parallel cohorts of MBM mice with FDA-approved protein translation inhibitor omacetaxine with or without CDK4/CDK6 inhibitor palbociclib, and monitored metastatic development and cell proliferation. Necropsies and IVIS imaging showed decreased MBM/extracranial metastasis in drug-treated mice, and RNA-Seq on mouse-blood-derived CTCs revealed downregulation of four RPL/RPS genes. However, mitochondrial stress tests and RT-qPCR showed that omacetaxine and palbociclib inversely affected glycolytic metabolism, demonstrating that dual targeting of cell translation/proliferation is critical to suppress plasticity in metastasis-competent CTCs. Equally relevant, we provide the first-ever functional metabolic characterization of patient-derived circulating neoplastic cells/CTCs.","journal":"Cancers","year":2023,"id":351913,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":563556,"name":"Seth D. Merkley","orcid":"0000-0002-4987-1195","position":1,"is_corresponding":false},{"id":1046394,"name":"Irina V. Lagutina","orcid":"0000-0001-9538-4008","position":2,"is_corresponding":false},{"id":1097462,"name":"Mireya C. Ortiz","orcid":null,"position":3,"is_corresponding":false},{"id":1096994,"name":"Margaret Lee","orcid":"0000-0003-0421-6290","position":4,"is_corresponding":false},{"id":817902,"name":"Bernard Tawfik","orcid":"0000-0002-4380-2471","position":5,"is_corresponding":false},{"id":406390,"name":"Dario Marchetti","orcid":"0000-0002-5951-2823","position":6,"is_corresponding":false},{"id":1086465,"name":"Tetiana Y. Bowley","orcid":"0000-0002-0172-169X","position":0,"is_corresponding":true}],"reference_count":94,"raw_metadata":null,"created_at":"2026-07-19T01:12:45.897709Z","pmid":"37958436","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":[]}