ArticleCancer medicine2021
Ppp6c deficiency accelerates K-ras
Article in Cancer medicine, 2021. 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, 12 citations in OpenAlex.
- Mechanistic Insights and Clinical Implications of ELK1 in Solid Tumors: A Narrative Review.Cells · 2025Review
- Functional Role of Protein Phosphatase-6 (Current medicinal chemistry · 2025Review
- Protein phosphatase 6 promotes stemness of colorectal cancer cells.Cancer science · 2024Article
- Protein phosphatase 6 activates NF-κB to confer sensitivity to MAPK pathway inhibitors inScience signaling · 2024Article
- Oncogenic K-RasFEBS open bio · 2024Article
- Protein phosphatase 6 regulates trametinib sensitivity, a mitogen-activated protein kinase kinase (MEK) inhibitor, by regulating MEK1/2-ERK1/2 signaling in canine melanoma cells.The Journal of veterinary medical science · 2023Article
- PP6 deficiency in mice with KRAS mutation and Trp53 loss promotes early death by PDAC with cachexia-like features.Cancer science · 2022Article
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Authors and funding
22 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundEffective treatments for cancer harboring mutant RAS are lacking. In Drosophila, it was reported that PP6 suppresses tumorigenicity of mutant RAS. However, the information how PP6 regulates oncogenic RAS in mammals is limited.
methodsWe examined the effects of PP6 gene (Ppp6c) deficiency on tongue tumor development in K (K-rasG12D)- and KP (K-rasG12D + Trp53-deficient)-inducible mice.
resultsMice of K and KP genotypes developed squamous cell carcinoma in situ in the tongue approximately 2 weeks after the induction of Ppp6c deficiency and was euthanized due to 20% loss of body weight. Transcriptome analysis revealed significantly different gene expressions between tissues of Ppp6c-deficient tongues and those of Ppp6c wild type, while Trp53 deficiency had a relatively smaller effect. We then analyzed genes commonly altered by Ppp6c deficiency, with or without Trp53 deficiency, and identified a group concentrated in KEGG database pathways defined as 'Pathways in Cancer' and 'Cytokine-cytokine receptor interaction'. We then evaluated signals downstream of oncogenic RAS and those regulated by PP6 substrates and found that in the presence of K-rasG12D, Ppp6c deletion enhanced the activation of the ERK-ELK1-FOS, AKT-4EBP1, and AKT-FOXO-CyclinD1 axes. Ppp6c deletion combined with K-rasG12D also enhanced DNA double-strand break (DSB) accumulation and activated NFκB signaling, upregulating IL-1β, COX2, and TNF.
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