ArticleOncogene2018
Oncogenic RAS-induced CK1α drives nuclear FOXO proteolysis.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- LAMB3 drives gastric cancer progression through SAMD4A-mediated degradation of PHLPP2 mRNA leading to sustained PI3K-Akt activation.British journal of cancer · 2026Article
- Multifaceted regulatory role of proline‑ and glutamine-rich splicing factor in tumors (Review).Molecular medicine reports · 2026Review
- Identification and validation of RAS signaling-related genes for prognostic prediction and immunological characterization in gastric cancer.Translational cancer research · 2025Article
- GRK2 kinases in the primary cilium initiate SMOOTHENED-PKA signaling in the Hedgehog cascade.PLoS biology · 2024Article
- Casein Kinase 1α-A Target for Prostate Cancer Therapy?Cancers · 2024Review
- MicroRNAs-associated with FOXO3 in cellular senescence and other stress responses.Biogerontology · 2024Review
- SFPQ promotes RAS-mutant cancer cell growth by modulating 5'-UTR mediated translational control of CK1α.NAR cancer · 2022Article
- FBXO7 triggers caspase 8-mediated proteolysis of the transcription factor FOXO4 and exacerbates neuronal cytotoxicity.The Journal of biological chemistry · 2021Article
- Resveratrol inhibits bile acid-induced gastric intestinal metaplasia via the PI3K/AKT/p-FoxO4 signalling pathway.Phytotherapy research : PTR · 2021Article
- Adenosine A2A receptor signaling promotes FoxO associated autophagy in chondrocytes.Scientific reports · 2021Article
- The role of FOXOs and autophagy in cancer and metastasis-Implications in therapeutic development.Medicinal research reviews · 2020Review
- MDMX inhibits casein kinase 1α activity and stimulates Wnt signaling.The EMBO journal · 2020Article
- Article
- CK1α-targeting inhibits primary and metastatic colorectal cancerTranslational cancer research · 2020Article
- A Ras-LSD1 axis activates PI3K signaling through PIK3IP1 suppression.Oncogenesis · 2020Article
- GLP-1/GLP-1R Signaling Regulates Ovarian PCOS-Associated Granulosa Cells Proliferation and Antiapoptosis by Modification of Forkhead Box Protein O1 Phosphorylation Sites.International journal of endocrinology · 2020Article
- Actionable Strategies to Target Multiple Myeloma Plasma Cell Resistance/Resilience to Stress: Insights From "Omics" Research.Frontiers in oncology · 2020Review
- Diagnostic model of combined ceRNA and DNA methylation related genes in esophageal carcinoma.PeerJ · 2020Article
- The kinase inhibitor SI113 induces autophagy and synergizes with quinacrine in hindering the growth of human glioblastoma multiforme cells.Journal of experimental & clinical cancer research : CR · 2019Article
- Smurfs in Protein Homeostasis, Signaling, and Cancer.Frontiers in oncology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Evasion of forkhead box O (FOXO) family of longevity-related transcription factors-mediated growth suppression is necessary to promote cancer development. Since somatic alterations or mutations and transcriptional dysregulation of the FOXO genes are infrequent in human cancers, it remains unclear how these tumour suppressors are eliminated from cancer cells. The protein stability of FOXO3A is regulated by Casein Kinase 1 alpha (CK1α) in an oncogenic RAS-specific manner, but whether this mode of regulation extends to related FOXO family members is unknown. Here we report that CK1α similarly destabilizes FOXO4 in RAS-mutant cells by phosphorylation at serines 265/268. The CK1α-dependent phosphoregulation of FOXO4 is primed, in part, by the PI3K/AKT effector axis of oncogenic RAS signalling. In addition, mutant RAS coordinately elevates proteasome subunit expression and proteolytic activity to eradicate nuclear FOXO4 proteins from RAS-mutant cancer cells. Importantly, dual inhibition of CK1α and the proteasome synergistically inhibited the growth of multiple RAS-mutant human cancer cell lines of diverse tissue origin by blockade of nuclear FOXO4 degradation and induction of caspase-dependent apoptosis. Our findings challenge the current paradigm that nuclear export regulates the proteolysis of FOXO3A/4 tumour suppressors in the context of cancer and illustrates how oncogenic RAS-mediated degradation of FOXOs, via post-translational mechanisms, blocks these important tumour suppressors.
Indexed as
Identifiers
What OpenQuestion holds
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.