{"doi":"10.1242/dmm.049652","title":"Activation of an actin signaling pathway in pre-malignant mammary epithelial cells by P-cadherin is essential for transformation","abstract":"Alterations in the expression or function of cell adhesion molecules have been implicated in all steps of tumor progression. Among those, P-cadherin is highly enriched in basal-like breast carcinomas, playing a central role in cancer cell self-renewal, collective cell migration and invasion. To establish a clinically relevant platform for functional exploration of P-cadherin effectors in vivo, we generated a humanized P-cadherin Drosophila model. We report that actin nucleators, Mrtf and Srf, are main P-cadherin effectors in fly. We validated these findings in a human mammary epithelial cell line with conditional activation of the SRC oncogene. We show that, prior to promoting malignant phenotypes, SRC induces a transient increase in P-cadherin expression, which correlates with MRTF-A accumulation, its nuclear translocation and the upregulation of SRF target genes. Moreover, knocking down P-cadherin, or preventing F-actin polymerization, impairs SRF transcriptional activity. Furthermore, blocking MRTF-A nuclear translocation hampers proliferation, self-renewal and invasion. Thus, in addition to sustaining malignant phenotypes, P-cadherin can also play a major role in the early stages of breast carcinogenesis by promoting a transient boost of MRTF-A-SRF signaling through actin regulation.","journal":"Disease Models & Mechanisms","year":2023,"id":347459,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"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":1000057,"name":"Sara Canato","orcid":"0000-0002-1102-0192","position":1,"is_corresponding":false},{"id":1000058,"name":"Tito T. Jesus","orcid":"0000-0001-6295-9979","position":2,"is_corresponding":false},{"id":1000059,"name":"Margarida Gonçalves","orcid":"0000-0003-1180-9270","position":3,"is_corresponding":false},{"id":1000060,"name":"Patrícia S. Guerreiro","orcid":"0000-0001-8972-3333","position":4,"is_corresponding":false},{"id":535154,"name":"Carla S. Lopes","orcid":"0000-0002-9950-8925","position":5,"is_corresponding":false},{"id":1000061,"name":"Isabel Meireles","orcid":"0000-0001-7348-8893","position":6,"is_corresponding":false},{"id":1000062,"name":"Eurico Morais‐de‐Sá","orcid":"0000-0003-3525-8231","position":7,"is_corresponding":false},{"id":1000063,"name":"Joana Paredes","orcid":"0000-0002-1076-1343","position":8,"is_corresponding":false},{"id":603342,"name":"Florence Janody","orcid":"0000-0003-4326-0163","position":9,"is_corresponding":false},{"id":1000056,"name":"Lídia Faria","orcid":"0000-0003-3283-2111","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T01:11:57.720122Z","pmid":"36808468","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":[]}