ArticleOncotarget2016
Crosstalk between the IGF-1R/AKT/mTORC1 pathway and the tumor suppressors p53 and p27 determines cisplatin sensitivity and limits the effectiveness of an IGF-1R pathway inhibitor.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- HIPK2 exhibits context dependent dualistic effects and combinatorial inhibition of HIPK2-NLK-MAPK11 axis manifests synergism against gastric cancer.Human cell · 2026Article
- Intermittent Fasting and Androgen Receptor Signaling in Prostate Cancer: Metabolic Crosstalk and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Bridging the divide: unveiling mutual immunological pathways of cancer and pregnancy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Stimulation of ROS Generation by Extract ofAntioxidants (Basel, Switzerland) · 2021Article
- IGF-1 Receptor Signaling Regulates Type II Pneumocyte Senescence and Resulting Macrophage Polarization in Lung Fibrosis.International journal of radiation oncology, biology, physics · 2021Article
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- MiR-505 suppressed the growth of hepatocellular carcinoma cells via targeting IGF-1R.Bioscience reports · 2019Article
- p27/Kip1 functions as a tumor suppressor and oncoprotein in osteosarcoma.Scientific reports · 2019Article
- Raddeanin A Induces Apoptosis and Cycle Arrest in Human HCT116 Cells through PI3K/AKT Pathway Regulation In Vitro and In Vivo.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- p53 promotes AKT and SP1-dependent metabolism through the pentose phosphate pathway that inhibits apoptosis in response to Nutlin-3a.Journal of molecular cell biology · 2018Article
- p53 and metabolism: from mechanism to therapeutics.Oncotarget · 2018Review
- MiR-30a-5p confers cisplatin resistance by regulating IGF1R expression in melanoma cells.BMC cancer · 2018Article
- NVP-BEZ235 synergizes cisplatin sensitivity in osteosarcoma.Oncotarget · 2018Article
- TIMP3 Overexpression Improves the Sensitivity of Osteosarcoma to Cisplatin by Reducing IL-6 Production.Frontiers in genetics · 2018Article
- HDAC inhibition as a treatment concept to combat temsirolimus-resistant bladder cancer cells.Oncotarget · 2017Article
- The IGF-1R/AKT pathway has opposing effects on Nutlin-3a-induced apoptosis.Cancer biology & therapy · 2017Article
- Insulin-Like Growth Factor (IGF) Pathway Targeting in Cancer: Role of the IGF Axis and Opportunities for Future Combination Studies.Targeted oncology · 2017Review
- The IGF-1R/AKT pathway determines cell fate in response to p53.Translational cancer research · 2016Article
- Soluble Egg Antigens of Schistosoma japonicum Induce Senescence of Activated Hepatic Stellate Cells by Activation of the FoxO3a/SKP2/P27 Pathway.PLoS neglected tropical diseases · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The insulin-like growth factor-1 receptor (IGF-1R) signaling pathway is aberrantly activated in multiple cancers and can promote proliferation and chemotherapy resistance. Multiple IGF-1R inhibitors have been developed as potential therapeutics. However, these inhibitors have failed to increase patient survival when given alone or in combination with chemotherapy agents. The reason(s) for the disappointing clinical effect of these inhibitors is not fully understood. Cisplatin (CP) activated the IGF-1R/AKT/mTORC1 pathway and stabilized p53 in osteosarcoma (OS) cells. p53 knockdown reduced IGF-1R/AKT/mTORC1 activation by CP, and IGF-1R inhibition reduced the accumulation of p53. These data demonstrate positive crosstalk between p53 and the IGF-1R/AKT/mTORC1 pathway in response to CP. Further studies showed the effect of IGF-1R inhibition on CP response is dependent on p53 status. In p53 wild-type cells treated with CP, IGF-1R inhibition increased p53s apoptotic function but reduced p53-dependent senescence, and had no effect on long term survival. In contrast, in p53-null/knockdown cells, IGF-1R inhibition reduced apoptosis in response to CP and increased long term survival. These effects were due to p27 since IGF-1R inhibition stabilized p27 in CP-treated cells, and p27 depletion restored apoptosis and reduced long term survival. Together, the results demonstrate 1) p53 expression determines the effect of IGF-1R inhibition on cancer cell CP response, and 2) crosstalk between the IGF-1R/AKT/mTORC1 pathway and p53 and p27 can reduce cancer cell responsiveness to chemotherapy and may ultimately limit the effectiveness of IGF-1R pathway inhibitors in the clinic.
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Registered trials
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