Tumor Biology

, Volume 36, Issue 6, pp 4519–4523 | Cite as

RETRACTED ARTICLE: Insulin-like growth factor 1 promotes growth of gastric cancer by inhibiting foxo1 nuclear retention

Research Article

Abstract

Gastric cancer (GC) is the fourth most common malignant human cancer. So far, the molecular mechanisms underlying the tumorigenesis of GC are not completely understood. Here, we reported significantly higher levels of serum insulin-like growth factor (IGF)-1 in GC patients and significantly higher levels of phosphorylated IGF-1 receptor (IGF-1R) in the GC specimen. Moreover, IGF-1 induced phosphorylation of IGF-1R and then phosphorylation of its downstream factor Akt in the GC cells. Further, IGF-1/Akt-induced forkhead box protein O1 (FoxO1) nuclear exclusion, but not IGF-1/Akt-induced mTOR phosphorylation, was essential for the augment in GC cell growth. Together, IGF-1/Akt/FoxO1 regulatory machinery appears to be a previously unappreciated signaling axis involved in the carcinogenesis of GC.

Keywords

Gastric cancer Insulin-like growth factor 1 (IGF-1) Akt mTOR FoxO1 Cancer growth 

Notes

Conflicts of interest

None

References

  1. 1.
    Zhao X, Li X, Yuan H. microRNAs in gastric cancer invasion and metastasis. Front Biosci. 2013;18:803–10.CrossRefGoogle Scholar
  2. 2.
    Liu G, Jiang C, Li D, Wang R, Wang W. MiRNA-34a inhibits EGFR-signaling-dependent MMP7 activation in gastric cancer. Tumour Biol. 2014;35:9801–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Mao D, Zhang Y, Lu H, Zhang H. Molecular basis underlying inhibition of metastasis of gastric cancer by anti-VEGFa treatment. Tumour Biol. 2014;35:8217–23.CrossRefPubMedGoogle Scholar
  4. 4.
    Ye Y, Zhou X, Li X, Tang Y, Sun Y, Fang J. Inhibition of epidermal growth factor receptor signaling prohibits metastasis of gastric cancer via downregulation of MMP7 and MMP13. Tumour Biol. 2014;35:10891–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Tognon CE, Sorensen PH. Targeting the insulin-like growth factor 1 receptor (IGF1R) signaling pathway for cancer therapy. Expert Opin Ther Targets. 2012;16:33–48.CrossRefPubMedGoogle Scholar
  6. 6.
    Ewing GP, Goff LW. The insulin-like growth factor signaling pathway as a target for treatment of colorectal carcinoma. Clin Colorectal Cancer. 2010;9:219–23.CrossRefPubMedGoogle Scholar
  7. 7.
    Tao Y, Pinzi V, Bourhis J, Deutsch E. Mechanisms of disease: signaling of the insulin-like growth factor 1 receptor pathway–therapeutic perspectives in cancer. Nat Clin Pract Oncol. 2007;4:591–602.CrossRefPubMedGoogle Scholar
  8. 8.
    Gross DN, van den Heuvel AP, Birnbaum MJ. The role of FoxO in the regulation of metabolism. Oncogene. 2008;27:2320–36.CrossRefPubMedGoogle Scholar
  9. 9.
    Xiao X, Gaffar I, Guo P, Wiersch J, Fischbach S, Peirish L, et al. M2 macrophages promote beta-cell proliferation by up-regulation of SMAD7. Proc Natl Acad Sci U S A. 2014;111:E1211–1220.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ding H, Zhu Y, Chu T, Wang S. Epidermal growth factor induces FoxO1 nuclear exclusion to activate MMP7-mediated metastasis of larynx carcinoma. Tumour Biol. 2014;35:9987–92.CrossRefPubMedGoogle Scholar
  11. 11.
    Pei J, Lou Y, Zhong R, Han B. MMP9 activation triggered by epidermal growth factor induced FoxO1 nuclear exclusion in non-small cell lung cancer. Tumour Biol. 2014;35:6673–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Yang S, Xu H, Yu S, Cao H, Fan J, Ge C, et al. Foxo1 mediates insulin-like growth factor 1 (IGF1)/insulin regulation of osteocalcin expression by antagonizing Runx2 in osteoblasts. J Biol Chem. 2011;286:19149–58.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Puig O, Tjian R. Nutrient availability and growth: regulation of insulin signaling by dFOXO/FOXO1. Cell Cycle. 2006;5:503–5.CrossRefPubMedGoogle Scholar
  14. 14.
    Machida S, Spangenburg EE, Booth FW. Forkhead transcription factor FoxO1 transduces insulin-like growth factor’s signal to p27Kip1 in primary skeletal muscle satellite cells. J Cell Physiol. 2003;196:523–31.CrossRefPubMedGoogle Scholar
  15. 15.
    Chen J, Huang Q, Wang F. Inhibition of FoxO1 nuclear exclusion prevents metastasis of glioblastoma. Tumour Biol. 2014;35:7195–200.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Gastroenterology, Shandong Provincial Qianfoshan HospitalShandong UniversityJinanChina
  2. 2.Shandong University School of MedicineJinanChina
  3. 3.Department of GastroenterologyProvincial Hospital Affiliated to Shandong UniversityJinanChina

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