ArticleCell death and differentiation2012
The AMPK stress response pathway mediates anoikis resistance through inhibition of mTOR and suppression of protein synthesis.
Article in Cell death and differentiation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 133 citations in OpenAlex.
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- Specific regulation of muscle protein metabolism in broilers by dietary fermented cottonseed meal.Frontiers in veterinary science · 2026Article
- The 4E-BPs as Translational Regulators in Neurological Disorders: Molecular Mechanisms and Therapeutic Potential.Molecular neurobiology · 2025Review
- Anoikis resistance and cancer.BMC cancer · 2025Review
- Pre-established ATF4 occupancy and chromatin organization instruct selective transcription activation during integrated stress response.Nature communications · 2025Article
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- Specific signaling pathways mediated programmed cell death in tumor microenvironment and target therapies.Discover oncology · 2025Review
- Insights into targeting LKB1 in tumorigenesis.Genes & diseases · 2025Review
- Rethinking AMPK: A Reversible Switch Fortifying Cancer Cell Stress-Resilience.The Yale journal of biology and medicine · 2025Review
- MDA-MB-231 breast cancer cells adapted to anchorage-independent growth reveal senescent-like phenotype and persistent downregulation of PD-L1 expression.Frontiers in oncology · 2025Article
- LKB1 biology: assessing the therapeutic relevancy of LKB1 inhibitors.Cell communication and signaling : CCS · 2024Review
- How do prolonged anchorage-free lifetimes strengthen non-small-cell lung cancer cells to evade anoikis? - A link with altered cellular metabolomics.Biological research · 2023Article
- Involvement of redox signalling in tumour cell dormancy and metastasis.Cancer metastasis reviews · 2023Review
- Glutamine synthetase regulates the immune microenvironment and cancer development through the inflammatory pathway.International journal of medical sciences · 2023Article
- The role of AMPK in cancer metabolism and its impact on the immunomodulation of the tumor microenvironment.Frontiers in immunology · 2023Review
- Inhibition of protein translation under matrix-deprivation stress in breast cancer cells.Frontiers in medicine · 2023Article
- Article
- Construction of a novel anoikis-related prognostic model and analysis of its correlation with infiltration of immune cells in neuroblastoma.Frontiers in immunology · 2023Article
- AMP-activated protein kinase promotes breast cancer stemness and drug resistance.Disease models & mechanisms · 2022Article
- Oxygen and metabolic reprogramming in the tumor microenvironment influences metastasis homing.Cancer biology & therapy · 2021Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Suppression of anoikis after detachment of cancer cells from the extracellular matrix is a key step during metastasis. Here we show that, after detachment, mouse embryonic fibroblasts (MEFs) transformed by K-Ras(V12) or ETV6-NTRK3 (EN) activate a transcriptional response overrepresented by genes related to bioenergetic stress and the AMP-activated protein kinase (AMPK) energy-sensing pathway. Accordingly, AMPK is activated in both transformed and non-transformed cells after detachment, and AMPK deficiency restores anoikis to transformed MEFs. However, AMPK activation represses the mTOR complex-1 (mTORC1) pathway only in transformed cells, suggesting a key role for AMPK-mediated mTORC1 inhibition in the suppression of anoikis. Consistent with this, AMPK-/- MEFs transformed by EN or K-Ras show sustained mTORC1 activation after detachment and fail to suppress anoikis. Transformed TSC1-/- MEFs, which are incapable of suppressing mTORC1, also undergo anoikis after detachment, which is reversed by mTORC1 inhibitors. Furthermore, transformed AMPK-/- and TSC1-/- MEFs both have higher total protein synthesis rates than wild-type controls, and translation inhibition using cycloheximide partially restores their anoikis resistance, indicating a mechanism whereby mTORC1 inhibition suppresses anoikis. Finally, breast carcinoma cell lines show similar detachment-induced AMPK/mTORC1 activation and restoration of anoikis by AMPK inhibition. Our data implicate AMPK-mediated mTORC1 inhibition and suppression of protein synthesis as a means for bioenergetic conservation during detachment, thus promoting anoikis resistance.
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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.