ArticleOncotarget2016
AMPK-mediated up-regulation of mTORC2 and MCL-1 compromises the anti-cancer effects of aspirin.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- The relationship between aspirin consumption and hepatocellular carcinoma: a systematic review and meta-analysis.European journal of medical research · 2023Pooled it
- The role of mTORC2/RICTOR in immune cells and inflammatory diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Review
- AMPK Alchemy: Therapeutic Potentials in Allergy, Aging, and Cancer.Biomolecules & therapeutics · 2024Review
- Hyperphosphorylation of BCL-2 family proteins underlies functional resistance to venetoclax in lymphoid malignancies.The Journal of clinical investigation · 2023Article
- UsingCells · 2023Review
- Exploring the mTOR Signalling Pathway and Its Inhibitory Scope in Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Impact of Aspirin Use on Outcomes in Patients With Hepatocellular Cancer: A Nationwide Analysis.World journal of oncology · 2023Article
- AMPK suppresses Th2 cell responses by repressing mTORC2.Experimental & molecular medicine · 2022Article
- Aspirin in Hepatocellular Carcinoma.Cancer research · 2021Review
- Review
- Blockade of AMPK-Mediated cAMP-PKA-CREB/ATF1 Signaling Synergizes with Aspirin to Inhibit Hepatocellular Carcinoma.Cancers · 2021Article
- Sinomenine Suppresses Development of Hepatocellular Carcinoma CellsFrontiers in molecular biosciences · 2021Article
- [Effect of aspirin on hepatocellular carcinoma and its related mechanism].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2020Review
- ASA Suppresses PGEPharmaceuticals (Basel, Switzerland) · 2020Article
- Targeting mTOR for cancer therapy.Journal of hematology & oncology · 2019Review
- Beyond a chemopreventive reagent, aspirin is a master regulator of the hallmarks of cancer.Journal of cancer research and clinical oncology · 2019Review
- Magnesium-sensitive upstream ORF controls PRL phosphatase expression to mediate energy metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Sestrin 2 confers primary resistance to sorafenib by simultaneously activating AKT and AMPK in hepatocellular carcinoma.Cancer medicine · 2018Article
- The role of mTOR-mediated signals during haemopoiesis and lineage commitment.Biochemical Society transactions · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AMP-activated protein kinase (AMPK) is an important energy sensor that may inhibit cell proliferation or promote cell survival during stresses. Besides cyclooxygenase, AMPK is another target of the nonsteroid anti-inflammatory agent aspirin. Preclinical and clinical investigations demonstrate that aspirin can inhibit several types of cancer such as colorectal adenomas and hepatocellular carcinoma (HCC). However, little is known about the cellular response to aspirin that may lead to aspirin resistance. Here, we show that aspirin induces the expression of MCL-1 in HepG2 and SW480 cells through AMPK-mTOR-Akt/ERK axis. Treatment of HepG2 and SW480 cells with aspirin leads to increased MCL-1 expression, Akt and ERK1/2 phosphorylation. Inhibition of Akt/MEK abrogates the induction of MCL-1 by aspirin. Aspirin activates AMPK, which in turn up-regulates mTORC2 activity, Akt, ERK1/2 phosphorylation and MCL-1 expression. MCL-1 knockdown sensitizes cancer cells to aspirin-induced apoptosis. Combination of aspirin and AMPK, Akt or MEK inhibitor results in more significant inhibition of cell proliferation and induction of apoptosis than single agent. Moreover, sorafenib blocks aspirin-induced MCL-1 up-regulation. Combination of aspirin and sorafenib leads to much more cell death and less cell proliferation than each drug alone. Treatment of HCC and colon cancer xenografts with both aspirin and sorafenib results in more significant tumor suppression than single agent. These data demonstrate that AMPK-mediated up-regulation of mTORC2 and MCL-1 may compromise the anticancer effects of aspirin. Combination of aspirin and sorafenib may be an effective regimen to treat HCC and colon cancer.
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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.