Periostin silencing suppresses the aggressive phenotype of thyroid carcinoma cells by suppressing the Akt/thyroid stimulating hormone receptor axis.

Abstract

Clinical evidence indicates that high periostin expression correlates with aggressive phenotype in thyroid carcinoma. However, the biological roles of periostin in thyroid carcinoma development and progression are still unclear. In this study, we explored the effects of periostin silencing on thyroid carcinoma cell growth, invasion, and tumorigenesis. We also studied the impact of periostin on the activation of phosphoinositide 3-kinase (PI3-K)/Akt signaling, which is involved in the pathogenesis of thyroid carcinoma. It was found that downregulation of periostin significantly inhibited the proliferation, colony formation, and invasion in both FTC-133 and BCPAP thyroid carcinoma cells. In vivo tumorigenic studies confirmed that periostin depletion retarded the growth of subcutaneous FTC-133 xenograft tumors, which was coupled with a significant decline in the percentage of Ki-67-positive proliferating cells. Western blot analysis demonstrated that periostin downregulation caused a marked inhibition of thyroid stimulating hormone receptor (TSHR) expression and Akt phosphorylation in FTC-133 and BCPAP cells. Co-expression of constitutively active Akt (CA-Akt) significantly reversed periostin-mediated downregulation of TSHR. Most importantly, overexpression of TSHR or CA-Akt rescued FTC-133 cells from periostin-induced growth and invasion suppression. Collectively, periostin regulates thyroid carcinoma growth and progression via the Akt/TSHR axis and represents a promising therapeutic target for this malignancy.