{"doi":"10.1016/j.jbc.2024.105680","title":"Short peptides based on the conserved regions of MIEN1 protein exhibit anticancer activity by targeting the MIEN1 signaling pathway","abstract":"Migration and invasion enhancer 1 (MIEN1) overexpression characterizes several cancers and facilitates cancer cell migration and invasion. Leveraging conserved immunoreceptor tyrosine-based activation motif and prenylation motifs within MIEN1, we identified potent anticancer peptides. Among them, bioactive peptides LA3IK and RP-7 induced pronounced transcriptomic and protein expression changes at sub-IC50 concentrations. The peptides effectively inhibited genes and proteins driving cancer cell migration, invasion, and epithelial-mesenchymal transition pathways, concurrently suppressing epidermal growth factor-induced nuclear factor kappa B nuclear translocation in metastatic breast cancer cells. Specifically, peptides targeted the same signal transduction pathway initiated by MIEN1. Molecular docking and CD spectra indicated the formation of MIEN1-peptide complexes. The third-positioned isoleucine in LA3IK and CVIL motif in RP-7 were crucial for inhibiting breast cancer cell migration. This is evident from the limited migration inhibition observed when MDA-MB-231 cells were treated with scrambled peptides LA3IK SCR and RP-7 SCR. Additionally, LA3IK and RP-7 effectively suppressed tumor growth in an orthotopic breast cancer model. Notably, mice tolerated high intraperitoneal (ip) peptide doses of 90 mg/Kg well, surpassing significantly lower doses of 5 mg/Kg intravenously (iv) and 30 mg/Kg intraperitoneally (ip) used in both in vivo pharmacokinetic studies and orthotopic mouse model assays. D-isomers of LA3IK and RP-7 showed enhanced anticancer activity compared to their L-isomers. D-LA3IK remained stable in mouse plasma for 24 h with 75% remaining, exhibiting superior pharmacokinetic properties over D/L-RP-7. In summary, our findings mark the first report of short peptides based on MIEN1 protein sequence capable of inhibiting cancer signaling pathways, effectively impeding cancer progression both in vitro and in vivo.","journal":"Journal of Biological Chemistry","year":2024,"id":441803,"datarank":0.363601570577936,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.034017883977503036,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.034017883977503036,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":4,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":896285,"name":"Priyanka P. Desai","orcid":"0009-0002-3376-3226","position":1,"is_corresponding":false},{"id":753674,"name":"Antariksh Tyagi","orcid":"0000-0002-4662-077X","position":2,"is_corresponding":false},{"id":1086116,"name":"Jana B. Lampe","orcid":null,"position":3,"is_corresponding":false},{"id":1254870,"name":"Yogesh Srivastava","orcid":"0000-0002-3331-2946","position":4,"is_corresponding":false},{"id":1197449,"name":"Michael Donkor","orcid":"0000-0002-5488-0328","position":5,"is_corresponding":false},{"id":305700,"name":"Harlan P. Jones","orcid":"0000-0003-3248-0355","position":6,"is_corresponding":false},{"id":434498,"name":"Sergei V. Dzyuba","orcid":"0000-0002-4835-5885","position":7,"is_corresponding":false},{"id":1255370,"name":"Eric Crossley","orcid":null,"position":8,"is_corresponding":false},{"id":7763,"name":"Noelle S. Williams","orcid":"0000-0003-1894-5742","position":9,"is_corresponding":false},{"id":290850,"name":"Jamboor K. Vishwanatha","orcid":"0000-0002-0266-6020","position":10,"is_corresponding":false},{"id":896286,"name":"Amit Kumar Tripathi","orcid":"0000-0002-3784-8799","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:01:11.152920Z","pmid":"38272230","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":[]}