ArticleCell reports2022
A nuclear cAMP microdomain suppresses tumor growth by Hippo pathway inactivation.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Decoding GPCR signaling reprogramming in cancer: molecular mechanisms and therapeutic implications.Molecular medicine (Cambridge, Mass.) · 2026Review
- PANK4 Regulates YAP to Modulate the Glycolytic Pathway in LEC for Driving LECs-EMT in Early Diabetic Cataract Pathogenesis.Investigative ophthalmology & visual science · 2026Article
- PDE4D drives rewiring of the MAPK pathway in BRAF-mutated melanoma resistant to MAPK inhibitors.Cell communication and signaling : CCS · 2024Article
- Differentially expressed genes associated with high metabolic tumor volume served as diagnostic markers and potential therapeutic targets for pancreatic cancer.Journal of translational medicine · 2024Article
- GRK2 mediated degradation of SAV1 initiates hyperplasia of fibroblast-like synoviocytes in rheumatoid arthritis.Acta pharmaceutica Sinica. B · 2024Article
- Distinct cAMP Signaling Microdomains Differentially Regulate Melanosomal pH and Pigmentation.The Journal of investigative dermatology · 2023Article
- cAMP-Dependent Signaling and Ovarian Cancer.Cells · 2022Review
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Authors and funding
19 authors.
Funding
Abstract
Cyclic AMP (cAMP) signaling is localized to multiple spatially distinct microdomains, but the role of cAMP microdomains in cancer cell biology is poorly understood. Here, we present a tunable genetic system that allows us to activate cAMP signaling in specific microdomains. We uncover a nuclear cAMP microdomain that activates a tumor-suppressive pathway in a broad range of cancers by inhibiting YAP, a key effector protein of the Hippo pathway, inside the nucleus. We show that nuclear cAMP induces a LATS-dependent pathway leading to phosphorylation of nuclear YAP solely at serine 397 and export of YAP from the nucleus with no change in YAP protein stability. Thus, nuclear cAMP inhibition of nuclear YAP is distinct from other known mechanisms of Hippo regulation. Pharmacologic targeting of specific cAMP microdomains remains an untapped therapeutic approach for cancer; thus, drugs directed at the nuclear cAMP microdomain may provide avenues for the treatment of cancer.
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