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Tumor Biology

, Volume 37, Issue 7, pp 9071–9076 | Cite as

Protein arginine methyltransferase 1 interacts with Gli1 and regulates its transcriptional activity

Original Article

Abstract

Protein arginine methylation, which is mediated by the protein arginine methyltransferases (PRMTs), is associated with numerous fundamental cellular processes. Our previous studies have shown that PRMT1 activated Hedgehog signaling in the esophageal squamous cell carcinoma (ESCC) cells and promoted the growth and migration of cancer cells. However, the detailed mechanisms are unknown. In this study, it was found that PRMT1 interacted with the transcriptional factor Gli1 (glioma-associated oncogene homolog 1) in ESCC cells. The DNA-binding domain (DBD) of Gli1 is responsible for its interaction with PRMT1. Moreover, PRMT1 promoted the methylation of Gli1, and knocking down the expression of PRMT1 impaired the transcriptional activity as well as the biological functions of Gli1. Taken together, our study demonstrated that PRMT1 is a positive regulator of Hedgehog signaling, and PRMT1 might be a therapeutic target for ESCC.

Keywords

PRMT1 Gli1 Methylation ESCC 

Notes

Compliance with ethical standards

Conflicts of interest

None

References

  1. 1.
    Rubin LL, de Sauvage FJ. Targeting the Hedgehog pathway in cancer. Nat Rev Drug Discov. 2006;5(12):1026–33.CrossRefPubMedGoogle Scholar
  2. 2.
    Guha M. Hedgehog inhibitor gets landmark skin cancer approval, but questions remain for wider potential. Nat Rev Drug Discov. 2012;11(4):257–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Minton K. Cell signalling: putting the brakes on sonic hedgehog. Nat Rev Mol Cell Biol. 2013;14(3):129.CrossRefPubMedGoogle Scholar
  4. 4.
    Eaton S. Multiple roles for lipids in the Hedgehog signalling pathway. Nat Rev Mol Cell Biol. 2008;9(6):437–45.CrossRefPubMedGoogle Scholar
  5. 5.
    Briscoe J, Therond PP, The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol. 2013;14(7):416–29.CrossRefPubMedGoogle Scholar
  6. 6.
    Zhu W et al. Correlation of hedgehog signal activation with chemoradiotherapy sensitivity and survival in esophageal squamous cell carcinomas. Jpn J Clin Oncol. 2011;41(3):386–93.CrossRefPubMedGoogle Scholar
  7. 7.
    Mizuarai S, Kawagishi A, Kotani H. Inhibition of p70S6K2 down-regulates Hedgehog/GLI pathway in non-small cell lung cancer cell lines. Mol Cancer. 2009;8:44.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Min S et al. The glioma-associated oncogene homolog 1 promotes epithelial—mesenchymal transition in human esophageal squamous cell cancer by inhibiting E-cadherin via Snail. Cancer Gene Ther. 2013;20(7):379–85.CrossRefPubMedGoogle Scholar
  9. 9.
    Isohata N et al. Hedgehog and epithelial-mesenchymal transition signaling in normal and malignant epithelial cells of the esophagus. Int J Cancer. 2009;125(5):1212–21.CrossRefPubMedGoogle Scholar
  10. 10.
    Yang Y, Bedford MT. Protein arginine methyltransferases and cancer. Nat Rev Cancer. 2013;13(1):37–50.CrossRefPubMedGoogle Scholar
  11. 11.
    Cha B et al. Methylation by protein arginine methyltransferase 1 increases stability of Axin, a negative regulator of Wnt signaling. Oncogene. 2011;30(20):2379–89.CrossRefPubMedGoogle Scholar
  12. 12.
    Joost S et al. GLI1 inhibition promotes epithelial-to-mesenchymal transition in pancreatic cancer cells. Cancer Res. 2012;72(1):88–99.CrossRefPubMedGoogle Scholar
  13. 13.
    Kuphal S et al. GLI1-dependent transcriptional repression of CYLD in basal cell carcinoma. Oncogene. 2011;30(44):4523–30.CrossRefPubMedGoogle Scholar
  14. 14.
    Paul P et al. Gli1 transcriptional activity is negatively regulated by AKT2 in neuroblastoma. Oncotarget. 2013;4(8):1149–57.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Singh RR et al. Sonic hedgehog signaling pathway is activated in ALK-positive anaplastic large cell lymphoma. Cancer Res. 2009;69(6):2550–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Lee J et al. Gli1 is a target of Sonic hedgehog that induces ventral neural tube development. Development. 1997;124(13):2537–52.PubMedGoogle Scholar
  17. 17.
    Dery U et al. A glycine-arginine domain in control of the human MRE11 DNA repair protein. Mol Cell Biol. 2008;28(9):3058–69.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Boisvert FM et al. The GAR motif of 53BP1 is arginine methylated by PRMT1 and is necessary for 53BP1 DNA binding activity. Cell Cycle. 2005;4(12):1834–41.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Department of Cardiothoracic Surgery, Changhai HospitalSecond Military Medical UniversityShanghaiChina
  2. 2.Department of Medical OncologyChangzheng Hospital, Second Military Medical UniversityShanghaiChina

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