6198

RPS6KB1

The epithelial-mesenchymal transition (EMT) plays a significant role in renal tubulointerstitial fibrosis (TIF), which is one of hallmark pathological feature of diabetic nephropathy (DN). Angiotensin II via its type-1 receptor AT1R is involved in the development of TIF. The purpose of our study was aimed to investigate the effect of silencing of AT1R on EMT and elucidate the possible mechanism underling these effects. EMT was induced by high glucose (HG) in human proximal tubular epithelial cell line HK-2 cells. The mRNA levels of AT1R were determined. The expression of AT1R was silenced by small interfering RNA (siRNA) technology and confirmed by quantitative real time PCR (qRT-PCR). After transfection with siAT1R, cell viability and expression levels of epithelial cell marker (epithelial (E)-cadherin), mesenchymal cell marker (alpha-smooth muscle actin (alpha-SMA)), four transcriptional factors (snail, slug, twist, and ZEB-1) were determined, as well as the roles of mechanistic target of rapamycin (mTOR)/p70S6K signaling pathway. The levels of AT1R were significantly higher after exposure to HG (P < 0.05). Transfection with siAT1R had no effect on cell viability, but reversed HG-induced EMT by up-regulation of E-cadherin expression and decrease of alpha-SMA, snail, and twist levels. MTOR/p70S6K signaling pathway was highly activated in HK-2 cells cultured under HG, but was inhibited by transfection with siAT1R. Our results suggest that silencing of AT1R inhibits EMT induced by HG in HK-2 cells via inactivation of mTOR/p70S6K signaling pathway. Silencing of AT1R might be a new strategy to treat DN.CI - Copyright (c) 2015 Elsevier Inc. All rights reserved.

Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer worldwide and a common cause of cancer-related death, with a 5-year survival rate of less than 60%. IL-6 has been suggested to play an important role in cancer metastasis, but its mechanism in HNSCC has not been fully clarified. p70S6K has been reported to induce epithelial-mesenchymal transition (EMT) of ovarian cancer, but its role in HNSCC remains unknown. In this study, we found that p70S6K and IL-6 were upregulated in high-metastatic HNSCC cell lines that underwent EMT when compared to paired low-metastatic cell lines. Overexpression of p70S6K promoted EMT and migration of HNSCC cells, while downregulation of p70S6K attenuated IL-6-induced EMT and cell migration. Furthermore, IL-6-induced p70S6K activation was attenuated by inhibitors of the PI3K/Akt/mTOR, MAPK/ERK, and JAK/STAT3 signaling pathways, suggesting that it located downstream of these pathways. These findings suggest that p70S6K promotes IL-6-induced EMT and metastasis of HNSCC. Targeting p70S6K for HNSCC therapy may benefit patients through the inhibition of tumor growth, as well as metastasis.