{"doi":"10.1091/mbc.e10-09-0739","title":"S100A4-induced cell motility and metastasis is restricted by the Wnt/β-catenin pathway inhibitor calcimycin in colon cancer cells","abstract":"The calcium-binding protein S100A4 is a central mediator of metastasis formation in colon cancer. S100A4 is a target gene of the Wnt/β-catenin pathway, which is constitutively active in the majority of colon cancers. In this study a high-throughput screen was performed to identify small-molecule compounds targeting the S100A4-promoter activity. In this screen calcimycin was identified as a transcriptional inhibitor of S100A4. In colon cancer cells calcimycin treatment reduced S100A4 mRNA and protein expression in a dose- and time-dependent manner. S100A4-induced cellular processes associated with metastasis formation, such as cell migration and invasion, were inhibited by calcimycin in an S100A4-specific manner. Calcimycin reduced β-catenin mRNA and protein levels despite the expression of Δ45-mutated β-catenin. Consequently, calcimycin inhibited Wnt/β-catenin pathway activity and the expression of prominent β-catenin target genes such as S100A4, cyclin D1, c-myc, and dickkopf-1. Finally, calcimycin treatment of human colon cancer cells inhibited metastasis formation in xenografted immunodeficient mice. Our results demonstrate that targeting the expression of S100A4 with calcimycin provides a functional strategy to restrict cell motility in colon cancer cells. Therefore calcimycin may be useful for studying S100A4 biology, and these studies may serve as a lead for the development of treatments for colon cancer metastasis.","journal":"Molecular Biology of the Cell","year":2011,"id":6056,"datarank":4.709102359755935,"base_score":4.770684624465665,"endowment":4.770684624465665,"self_citation_contribution":0.7156026936698499,"citation_network_contribution":3.993499666086085,"self_endowment_contribution":0.7156026936698499,"citer_contribution":3.993499666086085,"corpus_percentile":null,"corpus_rank":null,"citation_count":117,"citer_count":106,"citers_with_citation_signal":95,"citers_with_endowment":95,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0443,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2011-09-15","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":57314,"name":"Wolfgang Walther","orcid":"0000-0003-2360-1370","position":1,"is_corresponding":false},{"id":57315,"name":"Dominic Scudiero","orcid":null,"position":2,"is_corresponding":false},{"id":57316,"name":"Mike Selby","orcid":null,"position":3,"is_corresponding":false},{"id":57317,"name":"Jutta Aumann","orcid":null,"position":4,"is_corresponding":false},{"id":57318,"name":"Clara Lemos","orcid":"0000-0002-3604-3323","position":5,"is_corresponding":false},{"id":57319,"name":"Iduna Fichtner","orcid":null,"position":6,"is_corresponding":false},{"id":57320,"name":"Peter M. Schlag","orcid":null,"position":7,"is_corresponding":false},{"id":57321,"name":"Robert H. Shoemaker","orcid":"0000-0003-3608-1714","position":8,"is_corresponding":false},{"id":57322,"name":"Ulrike Stein","orcid":"0000-0001-7006-282X","position":9,"is_corresponding":false},{"id":57323,"name":"Dominic A. Scudiero","orcid":null,"position":10,"is_corresponding":false},{"id":57313,"name":"Ulrike Sack","orcid":null,"position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","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":[]}