ArticleSignal transduction and targeted therapy2020
IGF-1R inhibition induces MEK phosphorylation to promote survival in colon carcinomas.
Article in Signal transduction and targeted therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Pooled it
- Pdcd4-Rictor interaction suppresses mTORC2-PFKFB3 axis and tumorigenesis in NSCLC.Neoplasia (New York, N.Y.) · 2026Article
- Article
- Pdcd4-Rictor Interaction Suppresses PFKFB3 to inhibit Tumorigenesis.Research square · 2026Article
- Prognostic value of brown adipocyte-related genes in colorectal cancer: a multi-omics and Mendelian randomization study.Discover oncology · 2025Article
- IGF-1R inhibitors in cancer: A review of available evidence and future outlook.Critical reviews in oncology/hematology · 2025Review
- Translational Inhibition of Slug by Pdcd4 Contributes to Invasion Inhibition in Colorectal Cancer Cells.Cancer medicine · 2025Article
- The kinase PLK1 promotes Hedgehog signaling-dependent resistance to the antiandrogen enzalutamide in metastatic prostate cancer.Science signaling · 2025Article
- Advances in Targeted and Chemotherapeutic Strategies for Colorectal Cancer: Current Insights and Future Directions.Biomedicines · 2025Review
- Intermittent exercise alleviates MI-induced renal injury in mice via IGF-1.Frontiers in physiology · 2025Article
- Adipose-derived exosomes ameliorate skeletal muscle atrophy via miR-146a-5p/IGF-1R signaling.Journal of nanobiotechnology · 2024Article
- The Impact of Pdcd4, a Translation Inhibitor, on Drug Resistance.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Heterogeneity and interplay: the multifaceted role of cancer-associated fibroblasts in the tumor and therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Exogenous Metabolic Modulators Improve Response to Carboplatin in Triple-Negative Breast Cancer.Cells · 2024Article
- Phosphoproteomic analysis reveals changes in A-Raf-related protein phosphorylation in response to Toxoplasma gondii infection in porcine macrophages.Parasites & vectors · 2024Article
- Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes.World journal of clinical oncology · 2024Article
- Gemcitabine resistance in non-small cell lung cancer is mediated through activation of the PI3K/AKT/NF-κB pathway and suppression of ERK signaling by reactive oxygen species.Journal of biochemical and molecular toxicology · 2023Article
- Translocation of IGF-1R in endoplasmic reticulum enhances SERCA2 activity to trigger CaActa pharmaceutica Sinica. B · 2023Article
- TIMP1 promotes cell proliferation and invasion capability of right-sided colon cancers via the FAK/Akt signaling pathway.Cancer science · 2022Article
- The Novel IGF-1R Inhibitor PB-020 Acts Synergistically with Anti-PD-1 and Mebendazole against Colorectal Cancer.Cancers · 2022Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
The insulin-like growth factor 1 receptor (IGF-1R) governs several signaling pathways for cell proliferation, survival, and anti-apoptosis. Thus, targeting IGF-1R appears as a reasonable rationale for tumor treatment. However, clinical studies showed that inhibition of IGF-1R has very limited efficacy due to the development of resistance to IGF-1R blockade in tumor cells. Here, we discovered that prolonged treatment of colon cancer cells with IGF-1R inhibitors (BMS-754807 and GSK1838705A) stimulates p70 KDa ribosomal protein S6 kinase 1 (p70S6K1) activation, a well-known kinase signaling for cell survival. We also found that p70S6K1 activation by IGF-1R inhibition is independent of K-Ras and PIK3CA mutations that frequently occur in colon cancer. Besides the increased p70S6K1 phosphorylation, the phosphorylation of mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) was elevated in the cells treated with BMS-754807. Interestingly, the increases in MEK1/2 and p70S6K1 phosphorylation were also observed when cells were subjected to the treatment of AKT inhibitor or genetic knockdown of AKT2 but not AKT1, suggesting that AKT2 inhibition stimulates MEK1/2 phosphorylation to activate p70S6K1. Conversely, inhibition of MEK1/2 by MEK1/2 inhibitor (U0126) or knockdown of MEK1 and MEK2 by corresponding mek1 and mek2 siRNA enhanced AKT phosphorylation, indicating mutual inhibition between AKT and MEK. Furthermore, the combination of BMS-754807 and U0126 efficiently decreased the cell viability and increased cleaved caspase 3 and apoptosis in vitro and in vivo. Our data suggest that the treatment of colon tumor cells with IGF-1R inhibitors stimulates p70S6K1 activity via MEK1/2 to promote survival, providing a new strategy for colorectal cancer therapeutics.
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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.