ArticleOncogene2009
Inhibition of PI-3K restores nuclear p27Kip1 expression in a mouse model of Kras-driven lung cancer.
Article in Oncogene, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 48 citations in OpenAlex.
- The lncRNA, CyKILRb acts as a ceRNA for tumor suppressive microRNA to augment oncogenic phenotype via induction of PIK3R2/PIMolecular therapy. Nucleic acids · 2026Article
- The link of FOXO1 and FOXO4 transcription factors to development of the lens.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- Mitochondrial VDAC1 Silencing in Urethane-Induced Lung Cancer Inhibits Tumor Growth and Alters Cancer Oncogenic Properties.Cancers · 2024Article
- Genetic Screens Identify a Context-Specific PI3K/p27Kip1 Node Driving Extrahepatic Biliary Cancer.Cancer discovery · 2021Article
- CHUK/IKK-α loss in lung epithelial cells enhances NSCLC growth associated with HIF up-regulation.Life science alliance · 2019Article
- p27The Journal of pathology · 2019Article
- Expression of FOXP1 and FOXO3a in extrahepatic cholangiocarcinoma and the implications in clinicopathological significance and prognosis.OncoTargets and therapy · 2019Article
- Checkpoint Kinase 1 Expression Predicts Poor Prognosis in Nigerian Breast Cancer Patients.Molecular diagnosis & therapy · 2018Article
- Sex-related differences of urethane and sodium valproate effects on Ki-67 expression in urethane-induced lung tumors of mice.Experimental and therapeutic medicine · 2017Article
- FOXO Signaling Pathways as Therapeutic Targets in Cancer.International journal of biological sciences · 2017Review
- p27kip1 expression limits H-Ras-driven transformation and tumorigenesis by both canonical and non-canonical mechanisms.Oncotarget · 2016Article
- Independent and core pathways in oncogenic KRAS signaling.Expert review of proteomics · 2016Article
- FOXO transcription factors in cancer development and therapy.Cellular and molecular life sciences : CMLS · 2016Review
- Mutant AKT1-E17K is oncogenic in lung epithelial cells.Oncotarget · 2015Article
- Loss of p27Kip¹ promotes metaplasia in the pancreas via the regulation of Sox9 expression.Oncotarget · 2015Article
- Animal Models of Chemical Carcinogenesis: Driving Breakthroughs in Cancer Research for 100 Years.Cold Spring Harbor protocols · 2015Article
- Sphingomyelin Synthase 1 Regulates Neuro-2a Cell Proliferation and Cell Cycle Progression Through Modulation of p27 Expression and Akt Signaling.Molecular neurobiology · 2015Article
- Sodium Valproate Enhances the Urethane-Induced Lung Adenomas and Suppresses Malignization of Adenomas in Ovariectomized Female Mice.International journal of endocrinology · 2015Article
- Expression Profiling Identifies Bezafibrate as Potential Therapeutic Drug for Lung Adenocarcinoma.Journal of Cancer · 2015Article
- Targeting oncogenic KRAS in non-small cell lung cancer cells by phenformin inhibits growth and angiogenesis.American journal of cancer research · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Reduced expression of the CDK inhibitor p27(Kip1) (p27) in human lung cancer correlates with tumor aggressiveness and poor prognosis. However, the regulation of p27 expression and the role of p27 during lung cancer are poorly understood. Urethane-induced lung tumors in mice frequently harbor mutations in the Kras oncogene, and in this study, we use this model to address the regulation of p27 during tumorigenesis. The Ras effector Akt is known to regulate p27 mRNA abundance by phosphorylating and inactivating the FOXO transcription factors. Phosphorylated Akt and FOXO proteins were both increased in lung tumors, correlating with a reduction in p27 mRNA transcript. Akt also directly phosphorylates p27 and regulates its nuclear/cytoplasmic localization. Tumors showed a reduced nuclear/cytoplasmic ratio of p27 protein, together with an increase in phosphorylated Thr197 p27 in the cytoplasmic pool. Treatment of lung tumor-bearing mice with the phosphoinositol-3 kinase inhibitor LY294002 induced a rapid decrease in phosphorylated Akt and phosphorylated p27, concomitant with an increase in nuclear p27. Germline p27 deficiency accelerated both the growth and malignant progression of urethane-induced lung tumors, and did so in a cell autonomous manner, confirming a causal role of p27 in tumor suppression. These results show that p27 is a potent barrier to the growth and malignant progression of Kras-initiated lung tumors. Further, the reduction of nuclear p27 in tumors is mediated by oncogene signaling pathways, which can be reversed by pharmacological agents.
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.