{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Li Z"],"funding":["Cancer Research UK","Department of Defense Breakthrough Fellowship","Susan G. Komen","NCI","NHLBI NIH HHS","NIH Pathway to Independence","NCI NIH HHS","NIH","Department of Defense"],"pagination":["1321-1339"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8983597"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["82(7)"],"pubmed_abstract":["Constitutively active estrogen receptor α (ER/ESR1) mutations have been identified in approximately one-third of ER+ metastatic breast cancers. Although these mutations are known as mediators of endocrine resistance, their potential role in promoting metastatic disease has not yet been mechanistically addressed. In this study, we show the presence of ESR1 mutations exclusively in distant but not local recurrences in five independent breast cancer cohorts. In concordance with transcriptomic profiling of ESR1-mutant tumors, genome-edited ESR1 Y537S and D538G-mutant cell models exhibited a reprogrammed cell adhesive gene network via alterations in desmosome/gap junction genes and the TIMP3/MMP axis, which functionally conferred enhanced cell-cell contacts while decreasing cell-extracellular m"],"journal":["Cancer research"],"pubmed_title":["Hotspot ESR1 Mutations Are Multimodal and Contextual Modulators of Breast Cancer Metastasis."],"pmcid":["PMC8983597"],"funding_grant_id":["20411","R01 HL128297","R01 CA221303","SAC170078","P30CA047904","12011","W81XWH1910434","W81XWH1910499","K99 CA237736","F30CA203154","F30 CA250167","F30CA250167","SAC110021","P30 CA047904","BC160764","K99CA237736","R01CA221303","SAC160073","F30 CA203154"],"pubmed_authors":["Montanez MA","Troness B","Lee AV","Yates ME","Wagle N","Lucas PC","Zhang Q","Oesterreich S","Richer JK","Gertz J","Fumagalli C","Sundd P","Jank P","Carroll JS","Bahreini A","El-Ashry D","Tseng GC","Priedigkeit NM","Wu Y","Denkert C","Guerini-Rocco E","Karsten MM","Chen J","Cristofanilli M","Blohmer JU","Atkinson JM","Buluwela L","Park BH","Levine KM","Gerratana L","Li Z","Wallace CT","Tasdemir N","Watkins SC","Arnesen S","Zhang Y","Zhu L","Ali S","Nasrazadani A"],"additional_accession":[]},"is_claimable":false,"name":"Hotspot ESR1 Mutations Are Multimodal and Contextual Modulators of Breast Cancer Metastasis.","description":"Constitutively active estrogen receptor α (ER/ESR1) mutations have been identified in approximately one-third of ER+ metastatic breast cancers. Although these mutations are known as mediators of endocrine resistance, their potential role in promoting metastatic disease has not yet been mechanistically addressed. In this study, we show the presence of ESR1 mutations exclusively in distant but not local recurrences in five independent breast cancer cohorts. In concordance with transcriptomic profiling of ESR1-mutant tumors, genome-edited ESR1 Y537S and D538G-mutant cell models exhibited a reprogrammed cell adhesive gene network via alterations in desmosome/gap junction genes and the TIMP3/MMP axis, which functionally conferred enhanced cell-cell contacts while decreasing cell-extracellular m","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2026-05-31T17:59:44.596Z","creation":"2025-04-05T22:18:01.238Z"},"accession":"S-EPMC8983597","cross_references":{"pubmed":["35078818"],"doi":["10.1158/0008-5472.can-21-2576","10.1158/0008-5472.CAN-21-2576"]}}