Periostin, a signal transduction intermediate in TGF-β-induced EMT in U-87MG human glioblastoma cells, and its inhibition by anthocyanidins

• Published in: Oncotarget Vol. 9; no. 31; pp. 22023 - 22037
• Main Authors: Ouanouki, Amira, Lamy, Sylvie, Annabi, Borhane
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 24.04.2018
• Subjects: Research Paper; anthocyanidins; TGF-β; glioblastoma; periostin; EMT
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.25153

Periostin is a secreted protein that is highly expressed in glioblastoma cells as compared to normal brain tissue, and is therefore considered as a potential biomarker in therapeutic modalities. Its contribution in the cancer cells invasive phenotype is, however, poorly understood. This work investigates the role of periostin in U-87 MG glioblastoma cell invasion, cell migration and in Transforming Growth Factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT). Periostin gene silencing, using small interfering RNA, decreased TGF-β-induced mesenchymal marker expression of fibronectin and vimentin, partly through reduced Smad2, Akt and Fak phosphorylation as well as U-87 MG cell invasion and migration. The effects of anthocyanidins, the most abundant diet-derived flavonoids, were examined on periostin-mediated downstream signaling pathways. Anthocyanidins were found to decrease periostin expression whether added under pre-, co- or post-treatment conditions along with TGF-β, and altered the Akt and Fak signaling pathways. These effects were similar to Galunisertib (LY2157299), a small molecule inhibitor of the TGF-β receptor I kinase. Taken together, our data demonstrate that periostin acts as a central element in TGF-β-induced EMT, which can be prevented by diet-derived anthocyanidins.