Downregulation of signaling-active IGF-1 by dipeptidyl peptidase IV (DPP-IV)

Ching Ting Lin, Hsiang Yun Tang, Yu San Han, Hui Ping Liu, Shiu Feng Huang, Chia Hui Chien, John Shyy, Jeng Jian Chiu, Xin Chen

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Functioning as an extracellular protease, dipeptidyl peptidase IV (DPP-IV) preferentially cleaves the peptide bond after the penultimate proline residue. We report here that DPP-IV cleaves the first two amino acids from insulin-like growth factor 1 (IGF-1), revealed by mass spectrometry. The kinetic parameters of the proteolytic cleavage indicate that this reaction is physiologically relevant. Interestingly, truncated IGF-1 is less potent than the full-length protein in activating the IGF-1R, but binds more readily to IGF-binding protein 3 (IGFBP3). Quantitative RT-PCR showed that the level of DPP-IV mRNA is dramatically lower in lung squamous cell carcinoma tissues than in adjacent nonneoplastic lung tissues. However, this reduction was not observed in lung adenocarcinoma tissues. Our study suggests a possible link between IGF-1 and DPP-IV in cancer development in a specific tumor niche. A DPP-IV-related pathway may be important in mitigating IGF-1 signaling. Consequently, a robust IGF signaling pathway may accelerate early carcinogenesis in environments lacking DPP-IV.

Original languageEnglish
Pages (from-to)301-309
Number of pages9
JournalInternational Journal of Biomedical Science
Volume6
Issue number4
Publication statusPublished - Dec 1 2010
Externally publishedYes

Keywords

  • Dipeptidyl peptidase IV
  • IGF binding protein 3
  • IGF signaling pathway
  • Insulin-like growth factor-1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Lin, C. T., Tang, H. Y., Han, Y. S., Liu, H. P., Huang, S. F., Chien, C. H., Shyy, J., Chiu, J. J., & Chen, X. (2010). Downregulation of signaling-active IGF-1 by dipeptidyl peptidase IV (DPP-IV). International Journal of Biomedical Science, 6(4), 301-309.