Dataset Information

Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, ?₁-integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts.

ABSTRACT: The role of prolidase (PEPD) as a ligand of the epidermal growth factor receptor (EGFR) was studied in an experimental model of wound healing in cultured fibroblasts. The cells were treated with PEPD (1-100 nM) and analysis of cell viability, proliferation, migration, collagen biosynthesis, PEPD activity, and the expressions of EGFR, insulin-like growth factor 1 (IGF-1), and ?₁-integrin receptor including downstream signaling proteins were performed. It has been found that PEPD stimulated proliferation and migration of fibroblasts via activation of the EGFR-downstream PI3K/Akt/mTOR signaling pathway. Simultaneously, PEPD stimulated the expression of ?₁-integrin and IGF-1 receptors and proteins downstream to these receptors such as FAK, Grb2, and ERK1/2. Collagen biosynthesis was increased in control and "wounded" fibroblasts under PEPD treatment. The data suggest that PEPD-induced EGFR signaling may serve as a new attempt to therapy wound healing.

SUBMITTER: Baszanowska W

PROVIDER: S-EPMC7833428 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, β<sub>1</sub>-integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts.

Baszanowska Weronika W Misiura Magdalena M Oscilowska Ilona I Palka Jerzy J Miltyk Wojciech W

International journal of molecular sciences 20210119 2

The role of prolidase (PEPD) as a ligand of the epidermal growth factor receptor (EGFR) was studied in an experimental model of wound healing in cultured fibroblasts. The cells were treated with PEPD (1-100 nM) and analysis of cell viability, proliferation, migration, collagen biosynthesis, PEPD activity, and the expressions of EGFR, insulin-like growth factor 1 (IGF-1), and β<sub>1</sub>-integrin receptor including downstream signaling proteins were performed. It has been found that PEPD stimul ...[more]

PMID: 33477899

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Project description:Primary bone tumor, also known as osteosarcoma (OS), is the most common primary malignancy of bone in children and young adults. Current treatment protocols yield a 5-year survival rate of near 70% although approximately 80% of patients have metastatic disease at the time of diagnosis. However, long-term survival rates have remained virtually unchanged for nearly four decades, largely due to our limited understanding of the disease process. One major signaling pathway that has been implicated in human OS tumorigenesis is the insulin-like growth factor (IGF)/insulin-like growth factor-1 receptor (IGF1R) signaling axis. IGF1R is a heterotetrameric α2β2 receptor, in which the α subunits comprise the ligand binding site, whereas the β subunits are transmembrane proteins containing intracellular tyrosine kinase domains. Although numerous strategies have been devised to target IGF/IGF1R axis, most of them have failed in clinical trials due to the lack of specificity and/or limited efficacy. Here, we investigated whether a more effective and specific blockade of IGF1R activity in human OS cells can be accomplished by employing dominant-negative IGF1R (dnIGF1R) mutants. We engineered the recombinant adenoviruses expressing two IGF1R mutants derived from the α (aa 1-524) and β (aa 741-936) subunits, and found that either dnIGF1Rα and/or dnIGF1Rβ effectively inhibited cell migration, colony formation, and cell cycle progression of human OS cells, which could be reversed by exogenous IGF1. Furthermore, dnIGF1Rα and/or dnIGF1Rβ inhibited OS xenograft tumor growth in vivo, with the greatest inhibition of tumor growth shown by dnIGF1Rα. Mechanistically, the dnIGF1R mutants down-regulated the expression of PI3K/AKT and RAS/RAF/MAPK, BCL2, Cyclin D1 and most EMT regulators, while up-regulating pro-apoptotic genes in human OS cells. Collectively, these findings strongly suggest that the dnIGF1R mutants, especially dnIGF1Rα, may be further developed as novel anticancer agents that target IGF signaling axis with high specificity and efficacy.

Dataset Information

Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, ?₁-integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts.

Publications

Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, β<sub>1</sub>-integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts.

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Dataset Information

Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, ?1-integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts.

Publications

Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, β<sub>1</sub>-integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, ?₁-integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts.