ArticleBMC cancer2011
P27(Kip1), regulated by glycogen synthase kinase-3β, results in HMBA-induced differentiation of human gastric cancer cells.
Article in BMC cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Palonosetron, a 5-HT3 Receptor Antagonist, Induces G1 Cell Cycle Arrest and Autophagy in Gastric Cancer Cells.International journal of molecular sciences · 2025Article
- The plasticity of epithelial cells and its potential in the induced differentiation of gastric cancer.Cell death discovery · 2024Review
- Article
- Mitogen-activated protein kinase activator with WD40 repeats (MAWD) and MAWD-binding protein induce cell differentiation in gastric cancer.BMC cancer · 2015Article
- Candidate tumour suppressor CCDC19 regulates miR-184 direct targeting of C-Myc thereby suppressing cell growth in non-small cell lung cancers.Journal of cellular and molecular medicine · 2014Article
- IKK-β/NF-κB p65 mediates p27(Kip1) protein degradation in arsenite response.Biochemical and biophysical research communications · 2014Article
- Article
- Stat6 cooperates with Sp1 in controlling breast cancer cell proliferation by modulating the expression of p21(Cip1/WAF1) and p27 (Kip1).Cellular oncology (Dordrecht, Netherlands) · 2013Article
- DNA damage promotes herpes simplex virus-1 protein expression in a neuroblastoma cell line.Journal of neurovirology · 2013Article
- Polypeptide N-acetylgalactosaminyltransferase 2 regulates cellular metastasis-associated behavior in gastric cancer.International journal of molecular medicine · 2012Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGastric cancer is the second most common cause of global cancer-related mortality. Although dedifferentiation predicts poor prognosis in gastric cancer, the molecular mechanism underlying dedifferentiation, which could provide fundamental insights into tumor development and progression, has yet to be elucidated. Furthermore, the molecular mechanism underlying the effects of hexamethylene bisacetamide (HMBA), a recently discovered differentiation inducer, requires investigation and there are no reported studies concerning the effect of HMBA on gastric cancer.
methodsBased on the results of FACS analysis, the levels of proteins involved in the cell cycle or apoptosis were determined using western blotting after single treatments and sequential combinations of HMBA and LiCl. GSK-3β and proton pump were investigated by western blotting after up-regulating Akt expression by Ad-Akt infection. To investigate the effects of HMBA on protein localization and the activities of GSK-3β, CDK2 and CDK4, kinase assays, immunoprecipitation and western blotting were performed. In addition, northern blotting and RNase protection assays were carried out to determine the functional concentration of HMBA.
resultsHMBA increased p27(Kip1) expression and induced cell cycle arrest associated with gastric epithelial cell differentiation. In addition, treating gastric-derived cells with HMBA induced G0/G1 arrest and up-regulation of the proton pump, a marker of gastric cancer differentiation. Moreover, treatment with HMBA increased the expression and activity of GSK-3β in the nucleus but not the cytosol. HMBA decreased CDK2 activity and induced p27(Kip1) expression, which could be rescued by inhibition of GSK-3β. Furthermore, HMBA increased p27(Kip1) binding to CDK2, and this was abolished by GSK-3β inhibition.
conclusionsThe results presented herein suggest that GSK-3β functions by regulating p27(Kip1) assembly with CDK2, thereby playing a critical role in G0/G1 arrest associated with HMBA-induced gastric epithelial cell differentiation.
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