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BIRC5

It has been identified that insulin-like growth factor 1 (IGF-1) activated various pathways of the epithelial-mesenchymal transition (EMT) in a couple of tumors. At the same time, survivin is implicated in EMT of gastric cancer (GC). To date, the impact of survivin on IGF-1-mediated EMT of GC has not been featured. In this work, we used the immunohistochemistry and molecular and cellular experiments to investigate the existence and significance of IGF-1 and survivin. Our findings revealed that survivin protein can be observed in majority of samples in all GC samples. Importantly, survivin expression has an obvious association with GC stage, and metastasis. In vitro, GC cell line BGC823 was treated with different concentrations of IGF-1, resulting in the activation of p-ERK, p-AKT, survivin, and the expression of EMT biomarkers, including N-cadherin, MMP2, and Snail. However, the silencing of survivin eradicated the expression IGF-1-induced EMT biomarkers and affected the migration and invasion of BGC823 cells. In conclusion, IGF-1 signaling activated survivin expression and controlled the expression of EMT biomarkers in the development of GC. This study lays a new stage for the molecular therapy of GC patients in the clinical treatment.

cancer stem cells drive the metastatic cascade by undergoing epithelial to mesenchymal transition (EMT) and again mesenchymal to epithelial transition (MET). Using multiple breast cancer cell lines including cigarette smoke induced breast cancer cells and tumor derived primary cells from patient sample; we developed a breast cancer metastasis model and reported the existence of an adherent, distinct pre-metastatic phase, quiescent-breast cancer stem cells (Q-BCSCs) prior to attaining an EMT. SURVIVIN was found to be expressed in Q-BCSCs. Time dependant biphasic expression of SURVIVIN in Q-BCSCs reveals that Q-BCSCs is a pre-metastatic phase distinct from both epithelial and mesenchymal counterparts. SURVIVIN favours metastasis and up-regulates WNT/beta-CATENIN pathway in a PI3 K/AKT-dependant manner for self-renewal. Knockdown of SURVIVIN in Q-BCSCs lost the metastatic property of cells by inhibiting invasion, EMT-MET, PI3 K/AKT/WNT cascade, and induced apoptosis. Thus, our data suggest the existence of a novel pre-metastatic phase (Q-BCSCs) before EMT and SURVIVIN acts as a marker for Quiescent-BCSCs.

Proliferative vitreoretinopathy (PVR) is a common complication of open globe injury and the most common cause of failed retinal detachment surgery. The response by retinal pigment epithelial (RPE) cells liberated into the vitreous includes proliferation and migration; most importantly, epithelial to mesenchymal transition (EMT) of RPE plays a central role in the development and progress of PVR. For the first time, we show that knockdown of BIRC5, a member of the inhibitor of apoptosis protein family, using either lentiviral vector based CRISPR/Cas9 nickase gene editing or inhibition of survivin using the small-molecule inhibitor YM155, results in the suppression of EMT in RPE cells. Knockdown of survivin or inhibition of survivin significantly reduced TGFbeta-induced cell proliferation and migration. We further demonstrated that knockdown or inhibition of survivin attenuated the TGFbeta signaling by showing reduced phospho-SMAD2 in BIRC5 knockdown or YM155-treated cells compared to controls. Inhibition of the TGFbeta pathway using TGFbeta receptor inhibitor also suppressed survivin expression in RPE cells. Our studies demonstrate that survivin contributes to EMT by cross-talking with the TGFbeta pathway in RPE cells. Targeting survivin using small-molecule inhibitors may provide a novel approach to treat PVR disease.CI - Copyright (c) 2018 Elsevier Inc. All rights reserved.

Insulin-like growth factor-1 (IGF-1), a small polypeptide hormone similar to insulin in protein structures, has been identified as an activator of epithelial-mesenchymal transition (EMT) pathways in several types of cancers. As a member of the inhibitor of apoptosis protein (IAP) family, survivin is implicated in the EMT of some cancers. However, the role of survivin on IGF-1-mediated EMT of hepatocellular carcinoma (HCC) has not been clarified. In the present study, we demonstrated that survivin was involved in the EMT process induced by IGF-1 in HCC cell line SMMC7721. With administration of different concentrations of IGF-1, survivin mRNA and protein expression were significantly increased and stimulated EMT in the tested cell line, while the increased invasive and migratory abilities of HCC cells and activation of the EMT process induced by IGF-1 were reversed after silencing of survivin expression by transfecting small interfering RNA. This was further confirmed by the observation of morphological changes, the decrease of invasive and migratory abilities and the downregulation of EMT markers, N-cadherin, vimentin and Snail, and the upregulation of E-cadherin. In conclusion, survivin may play a vital role in the IGF-1 signaling pathway by mediating EMT in HCC through the upregulation of the expression of EMT markers, and the knockdown of survivin expression may suppress the metastasis of HCC, which may provide new insights for the molecular therapy of HCC patients in clinical treatment.