ArticleOncogene2012
Promotion of cytoplasmic mislocalization of p27 by Helicobacter pylori in gastric cancer.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Akt Signaling Pathway Is Activated in the Minor Salivary Glands of Patients with Primary Sjögren's Syndrome.International journal of molecular sciences · 2021Trial
- Oxidative Stress-Mediated RUNX3 Mislocalization Occurs Via Jun Activation Domain-Binding Protein 1 and Histone Modification.Applied biochemistry and biotechnology · 2024Article
- Deregulation of the cyclin-dependent kinase inhibitor p27 as a putative candidate for transformation inAIMS microbiology · 2023Article
- Prognostic Significance of p27 and Survivin in H. pylori Gastritis and Gastric Cancer.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- The Role and Clinical Implications of the Retinoblastoma (RB)-E2F Pathway in Gastric Cancer.Frontiers in oncology · 2021Review
- Characterization of oncogene suppressor marker expression in patients with submucosal gastric carcinoma.Molecular and clinical oncology · 2018Article
- KPT-330 inhibition of chromosome region maintenance 1 is cytotoxic and sensitizes chronic myeloid leukemia to Imatinib.Cell death discovery · 2018Article
- Article
- Prognostic Importance of Cell Cycle Regulators Cyclin D1 (Gastroenterology research and practice · 2016Article
- Regulation of p27American journal of cancer research · 2016Article
- Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer.Advances in experimental medicine and biology · 2016Review
- Article
- Immunohistochemically detected expression of Skp2, p27 kip1, and p-p27 (Thr187) in patients with cholangiocarcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- p27Kip1 inhibits the cell cycle through non-canonical G1/S phase-specific gatekeeper mechanism.Cell cycle (Georgetown, Tex.) · 2015Article
- A new tumour suppression mechanism by p27Kip1: EGFR down-regulation mediated by JNK/c-Jun pathway inhibition.The Biochemical journal · 2014Article
- Article
- Inhibitors of SCF-Skp2/Cks1 E3 ligase block estrogen-induced growth stimulation and degradation of nuclear p27kip1: therapeutic potential for endometrial cancer.Endocrinology · 2013Article
- Controlled access of p53 to the nucleus regulates its proteasomal degradation by MDM2.Molecular pharmaceutics · 2013Article
- Article
- Helicobacter pylori decreases p27 expression through the delta opioid receptor-mediated inhibition of histone acetylation within the p27 promoter.Cancer letters · 2012Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The cyclin-dependent kinase (CDK) inhibitor p27 has an important role in cell cycle regulation. Reduced expression of p27 is commonly associated with poor prognosis in many malignancies, including gastric cancer. Cytoplasmic p27 mislocalization may be an additional indicator of high-grade tumors and poor prognosis in cancer. As chronic infection by Helicobacter pylori is the most important risk factor for gastric cancer development, we evaluated the effects of H. pylori on p27 expression and localization in gastric cancer cells. Co-culture of gastric cells with H. pylori induced cytoplasmic p27 expression and reduced nuclear p27 expression in vitro. Cytoplasmic p27 expression was associated with and dependent upon phosphorylation of p27 at T157 and T198: wild-type p27 accumulated in the cytoplasm, but non-phosphorylatable mutants affecting T157 or T198 were nuclear in H. pylori-infected cells. These post-translational p27 changes were secondary to activation of cellular phosphoinositide-3 kinase (PI3K) and AKT signaling pathways, and dependent upon a functional H. pylori cag pathogenicity island. We investigated the clinical significance of cytoplasmic p27 mislocalization in 164 cases of resected gastric cancer in tissue microarrays. In 97 cases (59%), cytoplasmic p27 mislocalization was observed, and this was associated with increased mortality in multivariate analysis. These results show that H. pylori infection induces AKT/PI3K-mediated phosphorylation of p27 at T157 and T198 to cause cytoplasmic p27 mislocalization in gastric cancer, and that p27 mislocalization is an adverse prognostic feature in gastric cancer. This is the first demonstration of the translocation of a specific bacterial virulence factor that post-translationally regulates a host cell CDK inhibitor. This is of particular significance, because p27 has both tumor-suppressive and oncogenic activities, depending upon its subcellular localization. Cytoplasmic mislocalization of p27 induced by H. pylori may be an important mechanistic link between H. pylori infection and gastric carcinogenesis.
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