ArticleOncoTargets and therapy2013
AKT/mTOR substrate P70S6K is frequently phosphorylated in gallbladder cancer tissue and cell lines.
Article in OncoTargets and therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 32 citations in OpenAlex.
- Results of an abbreviated phase-II study with the Akt Inhibitor MK-2206 in Patients with Advanced Biliary Cancer.Scientific reports · 2015Trial
- p70S6K as a Potential Anti-COVID-19 Target: Insights from Wet Bench and In Silico Studies.Cells · 2024Article
- CKD-581 Downregulates Wnt/β-Catenin Pathway by DACT3 Induction in Hematologic Malignancy.Biomolecules & therapeutics · 2022Article
- Overview of current targeted therapy in gallbladder cancer.Signal transduction and targeted therapy · 2020Review
- Targeting gallbladder cancer: a pathway based perspective.Molecular biology reports · 2020Review
- Eukaryotic translation initiation factor 6 overexpression plays a major role in the translational control of gallbladder cancer.Journal of cancer research and clinical oncology · 2019Article
- PIM1 kinase promotes gallbladder cancer cell proliferation via inhibition of proline-rich Akt substrate of 40 kDa (PRAS40).Journal of cell communication and signaling · 2019Article
- Salinomycin enhances doxorubicin sensitivity through reversing the epithelial-mesenchymal transition of cholangiocarcinoma cells by regulating ARK5.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2017Article
- Small molecule inhibitor screening identifified HSP90 inhibitor 17-AAG as potential therapeutic agent for gallbladder cancer.Oncotarget · 2017Article
- A potent therapeutics for gallbladder cancer by combinatorial inhibition of the MAPK and mTOR signaling networks.Journal of gastroenterology · 2016Article
- Macrophage migration inhibitory factor - a therapeutic target in gallbladder cancer.BMC cancer · 2015Article
- Article
- Expression of insulin-like growth factor I receptor as a biomarker for predicting prognosis in biliary tract cancer patients.Molecular and clinical oncology · 2015Article
- Inhibition of mTOR pathway attenuates migration and invasion of gallbladder cancer via EMT inhibition.Molecular biology reports · 2014Article
- NOV is upregulated and promotes migration and invasion in bladder cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
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Authors and funding
7 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundGallbladder carcinoma is a highly malignant tumor and a public health problem in some parts of the world. It is characterized by a poor prognosis and its resistance to radio and chemotherapy. There is an urgent need to develop novel therapeutic alternatives for the treatment of gallbladder carcinoma. The mammalian target of the rapamycin (mTOR) signaling pathway is activated in about 50% of human malignancies, and its role in gallbladder carcinoma has previously been suggested. In the present study, we investigated the phosphorylation status of the mTOR substrate p70S6K in preneoplastic and neoplastic gallbladder tissues and evaluated the effect of three mTOR inhibitors on cell growth and migration in gallbladder carcinoma cell lines.
methodsImmunohistochemical staining of phospho-p70S6K was analyzed in 181 gallbladder carcinoma cases, classified according to lesion type as dysplasia, early carcinoma, or advanced carcinoma. Protein expression of AKT/mTOR members was also evaluated in eight gallbladder carcinoma cell lines by Western blot analysis. We selected two gallbladder carcinoma cell lines (G415 and TGBC-2TKB) to evaluate the effect of rapamycin, RAD001, and AZD8055 on cell viability, cell migration, and protein expression.
resultsOur results showed that phospho-p70S6K is highly expressed in dysplasia (66.7%, 12/18), early cancer (84.6%, 22/26), and advanced cancer (88.3%, 121/137). No statistical correlation was observed between phospho-p70S6K status and any clinical or pathological features, including age, gender, ethnicity, wall infiltration level, or histological differentiation (P < 0.05). In vitro treatment with rapamycin, RAD001, and AZD8055 reduced cell growth, cell migration, and phospho-p70S6K expression significantly in G-415 and TGBC-2TKB cancer cells (P < 0.001).
conclusionOur findings confirm the upregulation of this signaling pathway in gallbladder carcinoma and provide a rationale for the potential use of mTOR inhibitors as a therapeutic strategy for human gallbladder carcinoma.
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