title: Downregulation of Signaling-active IGF-1 by Dipeptidyl Peptidase IV (DPP-IV).
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.
authors.affiliation: Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Taiwan (ROC); ; School of Chinese Medicine, China Medical University, Taichung, Taiwan (ROC);
authors.forename: Ching-Ting
authors.initials: CT
authors.lastname: Lin
authors.forename: Hsiang-Yun
authors.initials: HY
authors.lastname: Tang
authors.forename: Yu-San
authors.initials: YS
authors.lastname: Han
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Liu
authors.forename: Shiu-Feng
authors.initials: SF
authors.lastname: Huang
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Chien
authors.forename: John
authors.initials: J
authors.lastname: Shyy
authors.forename: Jeng-Jian
authors.initials: JJ
authors.lastname: Chiu
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
keywords: IGF binding protein 3; IGF signaling pathway; dipeptidyl peptidase IV; insulin-like growth factor-1