{"doi":"10.1101/2022.10.23.513385","title":"STIM1 signals through NFAT independently of Orai1 and SOCE to regulate breast cancer cell migration","abstract":"ABSTRACT Store-operated calcium entry (SOCE) contributes to several physiological and pathological conditions including transcription, secretion, immunodeficiencies, and cancer. SOCE has been shown to be important for breast cancer cell migration where knockdown of SOCE components (STIM1 or Orai1) decreases cancer metastasis. Here we show unexpectedly that STIM1 knockout (KO) metastatic MDA-MB-231 breast cancer cells migrate faster and have enhance invasion capacity compared to parental cells. In contrast, Orai1-KO cells, which have similar levels of SOCE inhibition as STIM1-KO, migrate slower than the parental cell line. This shows that the enhanced migration phenotype of STIM1-KO cells is not due to the loss of a Ca 2+ entry through SOCE, rather it involves transcriptional remodeling. Interestingly, NFATC2 is significantly downregulated in STIM1-KO cells and overexpression of NFATC2 reversed the enhanced migration of STIM1-KO cells. This demonstrates that STIM1 modulates NFATC2 expression independently of its role in SOCE. SUMMARY STATEMENT Breast cancer cells migrate faster when the ER Ca 2+ sensor STIM1 in knocked out due to downregulation of NFAT1 expression independent of Ca 2+ influx.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":312610,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":728176,"name":"Fang Yu","orcid":"0000-0002-6653-6962","position":1,"is_corresponding":false},{"id":342113,"name":"F. David Horgen","orcid":"0000-0001-9409-3030","position":2,"is_corresponding":false},{"id":655752,"name":"Khaled Machaca","orcid":"0000-0001-6215-2411","position":3,"is_corresponding":false},{"id":656329,"name":"Ayat S. Hammad","orcid":null,"position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T00:33:36.072096Z","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":[]}