ArticleCell death & disease2017
Implication of 4E-BP1 protein dephosphorylation and accumulation in pancreatic cancer cell death induced by combined gemcitabine and TRAIL.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Repurposing colforsin daropate to treat MYC-driven high-grade serous ovarian carcinomas.Science signaling · 2024Article
- Combining gemcitabine and MSC delivering soluble TRAIL to target pancreatic adenocarcinoma and its stroma.Cell reports. Medicine · 2024Article
- Roles of Rictor alterations in gastrointestinal tumors (Review).Oncology reports · 2024Article
- Improved Antitumor Efficiency ofInternational journal of nanomedicine · 2024Article
- Extracellular Vesicles Inhibit the Response of Pancreatic Ductal Adenocarcinoma Cells to Gemcitabine and TRAIL Treatment.International journal of molecular sciences · 2022Article
- Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma: A Physiopathologic and Pharmacologic Review.Cancers · 2022Review
- Effects of Antibacterial Co-Cr-Mo-Cu Alloys on Osteoblast Proliferation, Differentiation, and the Inhibition of Apoptosis.Orthopaedic surgery · 2022Article
- Arctigenin inhibits human breast cancer cell proliferation, migratory and invasive abilities and epithelial to mesenchymal transition by targeting 4EBP1.Experimental and therapeutic medicine · 2021Article
- Cardamonin inhibits cell proliferation by caspase-mediated cleavage of Raptor.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Crosstalk of the Caspase Family and Mammalian Target of Rapamycin Signaling.International journal of molecular sciences · 2021Review
- Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges.Frontiers in immunology · 2021Review
- Decanoic acid inhibits mTORC1 activity independent of glucose and insulin signaling.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
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Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic cancer cells show varying sensitivity to the anticancer effects of gemcitabine. However, as a chemotherapeutic agent, gemcitabine can cause intolerably high levels of toxicity and patients often develop resistance to the beneficial effects of this drug. Combination studies show that use of gemcitabine with the pro-apoptotic cytokine TRAIL can enhance the inhibition of survival and induction of apoptosis of pancreatic cancer cells. Additionally, following combination treatment there is a dramatic increase in the level of the hypophosphorylated form of the tumour suppressor protein 4E-BP1. This is associated with inhibition of mTOR activity, resulting from caspase-mediated cleavage of the Raptor and Rictor components of mTOR. Use of the pan-caspase inhibitor Z-VAD-FMK indicates that the increase in level of 4E-BP1 is also caspase-mediated. ShRNA-silencing of 4E-BP1 expression renders cells more resistant to cell death induced by the combination treatment. Since the levels of 4E-BP1 are relatively low in untreated pancreatic cancer cells these results suggest that combined therapy with gemcitabine and TRAIL could improve the responsiveness of tumours to treatment by elevating the expression of 4E-BP1.
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Registered trials
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