ArticleeLife2023
Oncogenic PKA signaling increases c-MYC protein expression through multiple targetable mechanisms.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Clinical guideline for the diagnosis and treatment of fibrolamellar carcinoma.Hepatology (Baltimore, Md.) · 2026Article
- Review
- cAMP promotes acute lysosome biogenesis through TFEB nuclear import-export dynamics.bioRxiv : the preprint server for biology · 2025Article
- Selective HDAC6 inhibitor WT161 modulates the VLA-4/FAK pathway by inhibiting PKA activity in acute lymphoblastic leukemia.Scientific reports · 2025Article
- Article
- The cAMP-PKA signaling initiates mitosis by phosphorylating Bora.Nature communications · 2025Article
- The evolution of AKAPs and emergence of PKA isotype selective anchoring determinants.The Journal of biological chemistry · 2025Article
- DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming.Cancer discovery · 2025Article
- Translation regulation in response to stress.The FEBS journal · 2024Review
- Protein kinase A and local signaling in cancer.The Biochemical journal · 2024Review
- Proteo-metabolomics and patient tumor slice experiments point to amino acid centrality for rewired mitochondria in fibrolamellar carcinoma.Cell reports. Medicine · 2024Article
- The role of Aurora kinase A in hepatocellular carcinoma: Unveiling the intriguing functions of a key but still underexplored factor in liver cancer.Cell proliferation · 2024Review
- Integration of metabolic flux with hepatic glucagon signaling and gene expression profiles in the conscious dog.American journal of physiology. Endocrinology and metabolism · 2024Article
- cAMP signaling: a remarkably regional affair.Trends in biochemical sciences · 2024Review
- DNAJB1-PRKACA fusion neoantigens elicit rare endogenous T cell responses that potentiate cell therapy for fibrolamellar carcinoma.Cell reports. Medicine · 2024Article
- DNAJB1-PRKACA fusion protein-regulated LINC00473 promotes tumor growth and alters mitochondrial fitness in fibrolamellar carcinoma.PLoS genetics · 2024Article
- Recruitment of BAG2 to DNAJ-PKAc scaffolds promotes cell survival and resistance to drug-induced apoptosis in fibrolamellar carcinoma.Cell reports · 2024Article
- Discovery of a Cushing's syndrome protein kinase A mutant that biases signaling through type I AKAPs.Science advances · 2024Article
- Models of fibrolamellar carcinomas, tools for evaluation of a new era of treatments.Frontiers in immunology · 2024Review
- Chebulagic acid suppresses gastric cancer by inhibiting the AURKA/β-catenin/Wnt pathway.Frontiers in pharmacology · 2023Article
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 1 country.
Funding
Abstract
Genetic alterations that activate protein kinase A (PKA) are found in many tumor types. Yet, their downstream oncogenic signaling mechanisms are poorly understood. We used global phosphoproteomics and kinase activity profiling to map conserved signaling outputs driven by a range of genetic changes that activate PKA in human cancer. Two signaling networks were identified downstream of PKA: RAS/MAPK components and an Aurora Kinase A (AURKA)/glycogen synthase kinase (GSK3) sub-network with activity toward MYC oncoproteins. Findings were validated in two PKA-dependent cancer models: a novel, patient-derived fibrolamellar carcinoma (FLC) line that expresses a DNAJ-PKAc fusion and a PKA-addicted melanoma model with a mutant type I PKA regulatory subunit. We identify PKA signals that can influence both de novo translation and stability of the proto-oncogene c-MYC. However, the primary mechanism of PKA effects on MYC in our cell models was translation and could be blocked with the eIF4A inhibitor zotatifin. This compound dramatically reduced c-MYC expression and inhibited FLC cell line growth in vitro. Thus, targeting PKA effects on translation is a potential treatment strategy for FLC and other PKA-driven cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.