{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Boyd AL"],"funding":["CIHR"],"pagination":["10108"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12562877"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(20)"],"pubmed_abstract":["Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by limited treatment options and poor prognosis. Although immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have shown clinical promise, many TNBC patients exhibit resistance or limited response, underscoring the need to understand regulatory mechanisms of PD-L1 expression. Here, we performed a kinome-wide inhibitor screen using a HEK293A cell line stably expressing a NanoLuc-tagged PD-L1 construct lacking its endogenous promoter, to identify post-translational regulators of PD-L1 stability. We identified focal adhesion kinase (FAK) as a novel modulator of PD-L1. FAK inhibition significantly decreased PD-L1 levels in HEK293A cells but paradoxically increased PD-L1 expression in TNBC cell lines. Mechanistic"],"journal":["International journal of molecular sciences"],"pubmed_title":["Kinome-Wide Screening Identifies FAK as a Novel Post-Translational Regulator of PD-L1 Stability and Immune Evasion in Triple-Negative Breast Cancer."],"pmcid":["PMC12562877"],"funding_grant_id":["186142","148629"],"pubmed_authors":["Yang X","Kelly T","Khanal P","Hao Y","Ge A","Boyd AL"],"additional_accession":[]},"is_claimable":false,"name":"Kinome-Wide Screening Identifies FAK as a Novel Post-Translational Regulator of PD-L1 Stability and Immune Evasion in Triple-Negative Breast Cancer.","description":"Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by limited treatment options and poor prognosis. Although immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have shown clinical promise, many TNBC patients exhibit resistance or limited response, underscoring the need to understand regulatory mechanisms of PD-L1 expression. Here, we performed a kinome-wide inhibitor screen using a HEK293A cell line stably expressing a NanoLuc-tagged PD-L1 construct lacking its endogenous promoter, to identify post-translational regulators of PD-L1 stability. We identified focal adhesion kinase (FAK) as a novel modulator of PD-L1. FAK inhibition significantly decreased PD-L1 levels in HEK293A cells but paradoxically increased PD-L1 expression in TNBC cell lines. Mechanistic","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-05-14T03:19:19.931Z","creation":"2026-05-14T03:12:29.154Z"},"accession":"S-EPMC12562877","cross_references":{"pubmed":["41155402"],"doi":["10.3390/ijms262010108"]}}