Down‐regulation of PDGFRβ suppresses invasion and migration in osteosarcoma cells by influencing epithelial–mesenchymal transition. Issue 9 (3rd August 2020)

• Record Type: Journal Article
• Authors: Xing, Sining; Wang, Changdong; Tang, Huying; Guo, Jiaqi; Liu, Xing; Yi, Faping; Liu, Geli; Wu, Xiangmei
• Is Part Of: FEBS open bio. Volume 10:Issue 9(2020)
• Page Start: 1748
• Page End: 1757
• Publication Date: 2020-08-03
• Subjects: epithelial–mesenchymal transition -- invasion -- migration -- osteosarcoma -- PDGFRβ; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.12915
• Languages: English
• ISSNs: 2211-5463

Abstract

Abstract : Osteosarcoma (OS) is the most common malignant bone tumor primarily influencing children and adults. Approximately one‐fifth of patients have micrometastasis in the lungs when OS is diagnosed. Platelet‐derived growth factor receptor (PDGFR) beta (PDGFRβ) is a subtype of PDGFR. PDGFRβ has been noted to be highly expressed in OS cell lines and patient specimens, and is associated with metastasis and poor prognosis of OS. However, mechanistic insights into the exact role of PDGFRβ in OS pathogenesis and development are still lacking. Here we assessed the effects of PDGFRβ on invasive and migratory abilities, such as the epithelial–mesenchymal transition and phosphatidylinositol 3‐kinase (PI3K), Akt and mammalian target of rapamycin (mTOR) pathways in HOS cells. Depleting PDGFRβ resulted in reduced migration of HOS cells in the small interfering RNA duplexes specific for the PDGFRβ group compared with the mock and scramble‐treated groups in Transwell invasion assays. Using wound‐healing assays, we demonstrate the rate of wound healing in the PDGF‐BB‐stimulated group was higher compared with the mock‐treated group. Western blot showed that down‐regulation of PDGFRβ decreased the expression of stromal phenotype markers and phosphorylation pathway proteins (PI3K, AKT and mTOR), but the epithelial phenotype marker was increased in HOS cells. Treating HOS cells with PDGF‐BB revealed a treatment time‐dependent increase of phosphorylated, but not total, PI3K, AKT and mTOR. Taken together, we suggest that PDGFRβ plays an important role in OS invasion, migration and epithelial–mesenchymal transition by influencing the PI3K, Akt and mTOR pathways, hence highlighting PDGFRβ as a potential therapeutic target for OS. Abstract : Platelet‐derived growth factor receptor beta belongs to the tyrosine kinase family. Platelet‐derived growth factor receptor beta binds to its specific ligand and induces autophosphorylation to activate the downstream phosphatidylinositol 3‐kinase/AKT/mammalian target of rapamycin pathway. The activated pathway molecules then influence the epithelial–mesenchymal transition process by regulating the expression of epithelial–mesenchymal transition‐related proteins, and ultimately regulating tumor metastasis.