ArticleCell cycle (Georgetown, Tex.)2012
mTOR-independent 4E-BP1 phosphorylation is associated with cancer resistance to mTOR kinase inhibitors.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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Who cites it
54 citing papers in PubMed, 76 citations in OpenAlex.
- Colorectal cancer cells respond differentially to autophagy induced by tyrosine kinase inhibitors.Scientific reports · 2026Article
- Volatilomic response to targeted cancer therapy in vitro.Scientific reports · 2025Article
- Chemical Probes for Studying the Eukaryotic Translation Initiation Factor 4E (eIF4E)-Regulated Translatome in Cancer.ACS pharmacology & translational science · 2025Review
- Exploring the mTOR Signalling Pathway and Its Inhibitory Scope in Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Review
- CDK13 phosphorylates the translation machinery and promotes tumorigenic protein synthesis.Oncogene · 2023Article
- Dual Target of EGFR and mTOR Suppresses Triple-Negative Breast Cancer Cell Growth by Regulating the Phosphorylation of mTOR Downstream Proteins.Breast cancer (Dove Medical Press) · 2023Article
- Article
- Evidence for Bell-Shaped Dose-Response Emetic Effects of Temsirolimus and Analogs: The Broad-Spectrum Antiemetic Efficacy of a Large Dose of Temsirolimus Against Diverse Emetogens in the Least Shrew (Frontiers in pharmacology · 2022Article
- BAD regulates mammary gland morphogenesis by 4E-BP1-mediated control of localized translation in mouse and human models.Nature communications · 2021Article
- STAT3-mediated MLST8 gene expression regulates cap-dependent translation in cancer cells.Molecular oncology · 2020Article
- Cyclin-dependent kinase 4 inhibits the translational repressor 4E-BP1 to promote cap-dependent translation during mitosis-G1 transition.FEBS letters · 2020Article
- Impaired TFEB-mediated lysosomal biogenesis promotes the development of pancreatitis in mice and is associated with human pancreatitis.Autophagy · 2019Article
- Chemoproteomic Profiling Uncovers CDK4-Mediated Phosphorylation of the Translational Suppressor 4E-BP1.Cell chemical biology · 2019Article
- mTOR Signaling in Cancer and mTOR Inhibitors in Solid Tumor Targeting Therapy.International journal of molecular sciences · 2019Review
- Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson's disease.Translational neurodegeneration · 2019Review
- Review
- Inhibition of mTORC1/C2 signaling improves anti-leukemia efficacy of JAK/STAT blockade inOncotarget · 2018Article
- RAPTOR up-regulation contributes to resistance of renal cancer cells to PI3K-mTOR inhibition.PloS one · 2018Article
- K-Ras mutation and amplification status is predictive of resistance and high basal pAKT is predictive of sensitivity to everolimus in biliary tract cancer cell lines.Molecular oncology · 2017Article
- Focal Adhesion- and IGF1R-Dependent Survival and Migratory Pathways Mediate Tumor Resistance to mTORC1/2 Inhibition.Molecular cell · 2017Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
ATP-competitive mTOR kinase inhibitors (mTorKIs) are a new generation of mTOR-targeted agents with more potent anticancer activity than rapamycin in several tumor models. However, the sensitivity and resistance of cancer cells to mTorKIs remain poorly understood. In this study, we tested mTorKIs against a large panel of colorectal cancer (CRC) cell lines, and found that mTorKIs displayed broader anti-CRC activity than rapamycin, including CRC cells with K-Ras or B-Raf mutations, suggesting that these mTorKIs are particularly useful for CRCs resistant to EGFR inhibitors. Unexpectedly, we found that 40% CRC cell lines were intrinsically drug resistant. Moreover, we discovered an mTOR-independent 4E‑BP1 phosphorylation that was correlated with mTorKI resistance. Altogether, our findings provide compelling preclinical support for testing mTorKIs in human CRC clinical trials. They further reveal the existence of significant intrinsic mTorKI drug resistance in cancer cells and suggest that 4E-BP1 phosphorylation is a predictive biomarker for mTorKI sensitivity and resistance.
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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.