{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Simpson CL"],"funding":["National Institute of Arthritis and Musculoskeletal and Skin Diseases","NCATS NIH HHS","Foundation for Ichthyosis and Related Skin Types","Physician-Scientist Support Fund","Taubman Medical Research Institute","NIAMS NIH HHS","University of Washington Institute for Stem Cell and Regenerative Medicine"],"pagination":["e182983"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11601706"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(21)"],"pubmed_abstract":["Grover disease is an acquired epidermal blistering disorder in which keratinocytes lose intercellular connections. While its pathologic features are well defined, its etiology remains unclear, and there is no FDA-approved therapy. Interestingly, Grover disease was a common adverse event in clinical trials for cancer using B-RAF inhibitors, but it remained unknown how B-RAF blockade compromised skin integrity. Here, we identified ERK hyperactivation as a key driver of Grover disease pathology. We leveraged a fluorescent biosensor to confirm that the B-RAF inhibitors dabrafenib and vemurafenib paradoxically activated ERK in human keratinocytes and organotypic epidermis, disrupting cell-cell junctions and weakening epithelial integrity. Consistent with clinical data showing that concomitant M"],"journal":["JCI insight"],"pubmed_title":["ERK hyperactivation in epidermal keratinocytes impairs intercellular adhesion and drives Grover disease pathology."],"pmcid":["PMC11601706"],"funding_grant_id":["N/A","P30 AR069589","NIH P30-AR069589","Innovation Pilot Award","R03 TR005428","NIH R03-AR082896","Research Grant","K08 AR075846","NIH K08-AR075846","NIH P30-AR075043","R03 AR082896","Medical Scholars Research Fellowship","P30 AR075043"],"pubmed_authors":["Tiwaa A","Gudjonsson JE","Harms PW","Simpson CL","Zaver SA","Chu EY","Johnson CJ"],"additional_accession":[]},"is_claimable":false,"name":"ERK hyperactivation in epidermal keratinocytes impairs intercellular adhesion and drives Grover disease pathology.","description":"Grover disease is an acquired epidermal blistering disorder in which keratinocytes lose intercellular connections. While its pathologic features are well defined, its etiology remains unclear, and there is no FDA-approved therapy. Interestingly, Grover disease was a common adverse event in clinical trials for cancer using B-RAF inhibitors, but it remained unknown how B-RAF blockade compromised skin integrity. Here, we identified ERK hyperactivation as a key driver of Grover disease pathology. We leveraged a fluorescent biosensor to confirm that the B-RAF inhibitors dabrafenib and vemurafenib paradoxically activated ERK in human keratinocytes and organotypic epidermis, disrupting cell-cell junctions and weakening epithelial integrity. Consistent with clinical data showing that concomitant M","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Nov","modification":"2025-04-04T02:39:00.895Z","creation":"2025-04-04T02:39:00.895Z"},"accession":"S-EPMC11601706","cross_references":{"pubmed":["39325541"],"doi":["10.1172/jci.insight.182983"]}}