{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yang X"],"funding":["National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["613"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12820175"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(1)"],"pubmed_abstract":["Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease with limited therapies. While UFL1-mediated UFMylation has been implicated in various diseases, its role in TNBC remains not fully understood. Here, we demonstrate that AKT1 directly interacts with UFL1 and undergoes UFMylation at Lys189/276/297. This modification enhances AKT phosphorylation and activation, promoting tumor growth and chemoresistance in TNBC. In turn, AKT phosphorylates UFL1 at Thr426, establishing a positive feedback loop that sustains high activity of both pro-oncogenic regulators in TNBC. Disrupting the UFL1-AKT interaction using the specific peptide PDAU-TAT significantly inhibits TNBC progression both in vitro and in vivo. Clinically, elevated pT426 UFL1 correlates with high pAKT in TNBC specimens. These findings uncover a crucial UFL1-AKT positive feedback loop that drives TNBC progression and suggest that targeting this axis could offer a promising therapeutic strategy for TNBC and potentially other aggressive cancers characterized by upregulated UFL1 and AKT activation."],"journal":["Nature communications"],"pubmed_title":["Targeting the UFL1-AKT cascade suppresses triple-negative breast cancer progression."],"pmcid":["PMC12820175"],"funding_grant_id":["82473109","82404654"],"pubmed_authors":["Yang X","Wen Y","Liu Y","Chen J","Zhang H","Ma X","Liu T","Qin S","Goding CR","Cui R"],"additional_accession":[]},"is_claimable":false,"name":"Targeting the UFL1-AKT cascade suppresses triple-negative breast cancer progression.","description":"Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease with limited therapies. While UFL1-mediated UFMylation has been implicated in various diseases, its role in TNBC remains not fully understood. Here, we demonstrate that AKT1 directly interacts with UFL1 and undergoes UFMylation at Lys189/276/297. This modification enhances AKT phosphorylation and activation, promoting tumor growth and chemoresistance in TNBC. In turn, AKT phosphorylates UFL1 at Thr426, establishing a positive feedback loop that sustains high activity of both pro-oncogenic regulators in TNBC. Disrupting the UFL1-AKT interaction using the specific peptide PDAU-TAT significantly inhibits TNBC progression both in vitro and in vivo. Clinically, elevated pT426 UFL1 correlates with high pAKT in TNBC specimens. These findings uncover a crucial UFL1-AKT positive feedback loop that drives TNBC progression and suggest that targeting this axis could offer a promising therapeutic strategy for TNBC and potentially other aggressive cancers characterized by upregulated UFL1 and AKT activation.","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-06-06T18:08:50.269Z","creation":"2026-06-04T03:10:35.284Z"},"accession":"S-EPMC12820175","cross_references":{"pubmed":["41559059"],"doi":["10.1038/s41467-026-68493-2"]}}