ArticleOncotarget2015
Inhibition of insulin-like growth factor receptor/AKT/mammalian target of rapamycin axis targets colorectal cancer stem cells by attenuating mevalonate-isoprenoid pathway in vitro and in vivo.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Meta-Analysis of Altered Gut Microbiota Reveals Microbial and Metabolic Biomarkers for Colorectal Cancer.Microbiology spectrum · 2022Pooled it
- Serum Chemerin Concentrations and Tissue Immunoreactivity in Colorectal Adenoma and Colorectal Cancer: An Exploratory Case-Control Study.Diagnostics (Basel, Switzerland) · 2026Article
- StarD5 Regulates Cholesterol Homeostasis to Promote Colorectal Cancer Progression and the Cancer Stem Cell Phenotype.Molecular cancer research : MCR · 2026Article
- Lipid metabolism in cancer stem cells: reprogramming, mechanisms, crosstalk, and therapeutic approaches.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Simvastatin-Mediated Molecular Mechanisms Underlying the Growth Inhibition of Testicular Leydig Tumour Cells.Journal of cellular and molecular medicine · 2025Article
- Targeting Lipid Metabolism in Cancer Stem Cells for Anticancer Treatment.International journal of molecular sciences · 2024Review
- Lipid metabolism dynamics in cancer stem cells: potential targets for cancers.Frontiers in pharmacology · 2024Review
- Article
- Designing Synthetic, Sulfated Glycosaminoglycan Mimetics That Are Orally Bioavailable and ExhibitingJournal of medicinal chemistry · 2023Article
- Cholesterol in colorectal cancer: an essential but tumorigenic precursor?Frontiers in oncology · 2023Review
- Glycan Modulation of Insulin-like Growth Factor-1 Receptor.Angewandte Chemie (International ed. in English) · 2022Article
- Review
- Lipid metabolism within the bone micro-environment is closely associated with bone metabolism in physiological and pathophysiological stages.Lipids in health and disease · 2022Review
- TMED3/RPS15A Axis promotes the development and progression of osteosarcoma.Cancer cell international · 2021Article
- Pongol Methyl Ether Inhibits Akt and Suppresses Cancer Stem Cell Phenotypes in Lung Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2021Article
- HSPA4 Knockdown Retarded Progression and Development of Colorectal Cancer.Cancer management and research · 2021Article
- Metabolic and behavioral features of acute hyperpurinergia and the maternal immune activation mouse model of autism spectrum disorder.PloS one · 2021Article
- Associations of cholesterol and vitamin D metabolites with the risk for development of high grade colorectal cancer.Journal of medical biochemistry · 2020Article
- FDPS cooperates with PTEN loss to promote prostate cancer progression through modulation of small GTPases/AKT axis.Oncogene · 2019Article
- The role of cholesterol metabolism in cancer.American journal of cancer research · 2019Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
We observed a co-upregulation of the insulin-like growth factor receptor (IGF-1R)/AKT/mammalian target of rapamycin (mTOR) [InAT] axis and the mevalonate-isoprenoid biosynthesis (MIB) pathways in colorectal cancer stem cells (CSCs) in an unbiased approach. Hence, we hypothesized that the InAT axis might regulate the MIB pathway to govern colorectal CSCs growth. Stimulation (IGF-1) or inhibition (IGF-1R depletion and pharmacological inhibition of IGF-1R/mTOR) of the InAT axis produced induction or attenuation of CSC growth as well as expression of CSC markers and self-renewal factors respectively. Intriguingly, activation of the InAT axis (IGF-1) caused significant upregulation of the MIB pathway genes (both mRNA and protein); while its inhibition produced the opposite effects in colonospheres. More importantly, supplementation with dimethylallyl- and farnesyl-PP, MIB metabolites downstream of isopentenyl-diphosphate delta isomerase (IDI), but not mevalonate and isopentenyl-pp that are upstream of IDI, resulted in a near-complete reversal of the suppressive effect of the InAT axis inhibitors on CSCs growth. The latter findings suggest a specific regulation of the MIB pathway by the InAT axis distal to the target of statins that inhibit 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Effects of IGF-1R inhibition on colonic CSCs proliferation and the MIB pathway were confirmed in an 'in vivo' HCT-116 xenograft model. These observations establish a novel mechanistic link between the InAT axis that is commonly deregulated in colorectal cancer and the MIB pathway in regulation of colonic CSCs growth. Hence, the InAT-MIB corridor is a novel target for developing paradigm shifting optimum anti-CSCs therapies for colorectal cancer.
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