ArticleGenome biology2026
Ubiquitination degradation of GATA4 by CUL4B promotes ovarian cancer metastasis by inducing lysosomal acidification.
Article in Genome biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
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11 authors.
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Abstract
backgroundOvarian cancer remains highly lethal due to late-stage diagnosis and aggressive metastatic potential. Lysosomal acidification plays a critical role in tumor metastasis, regulated by multiple genetic factors. While GATA4 is a well-established transcriptional activator in cardiomyogenesis, its function in carcinogenesis remains ambiguous, particularly in ovarian cancer, and its impact on lysosomal regulation is poorly understood. Therefore, we aim to elucidate the function of GATA4 in ovarian cancer metastasis and the underlying molecular mechanisms.
resultsWe find that downregulation of GATA4 in ovarian cancer correlates with enhanced lysosomal acidification, increased cell proliferation, and elevated lung and abdominal metastasis both in vitro and in vivo. Mechanistically, GATA4 interacts with the CRL4B complex and undergoes CUL4B-mediated ubiquitination at lysine residues 329 and 404. Integrated RNA-seq and CUT&Tag, ChIP-qPCR, and dual-luciferase assays reveal that GATA4 activates H3K27ac modification at tumor suppressor gene TRIM22, consequently modulating epithelial-mesenchymal transition and lysosomal acidification. These findings demonstrate that GATA4 suppresses lysosomal acidification and epithelial-mesenchymal transition, while its CRL4B-mediated ubiquitination and degradation in metastatic ovarian cancer cells leads to reduced H3K27ac modification at tumor suppressor genes.
conclusionsOur study elucidates the tumor-suppressive role of GATA4 in regulating lysosomal acidification and epithelial-mesenchymal transition through ubiquitination-dependent mechanisms and histone acetylation modulation. The findings identify GATA4 as a promising therapeutic target and diagnostic marker for ovarian cancer intervention.
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