Periostin, a signal transduction intermediate in TGF-β-induced EMT in U-87MG human glioblastoma cells, and its inhibition by anthocyanidins
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Amira Ouanouki1, Sylvie Lamy1 and Borhane Annabi1
1Laboratoire d’Oncologie Moléculaire, Centre de Recherche BioMed, Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, Québec, Canada H3C 3P8
Borhane Annabi, email: [email protected]
Keywords: anthocyanidins; EMT; glioblastoma; periostin; TGF-β
Received: May 07, 2017 Accepted: April 04, 2018 Published: April 24, 2018
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.
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