Knockdown of BAG3 induces epithelial–mesenchymal transition in thyroid cancer cells through ZEB1 activation

Abstract

The process by which epithelial features are lost in favor of a mesenchymal phenotype is referred to as epithelial–mesenchymal transition (EMT). Most carcinomas use this mechanism to evade into neighboring tissues. Reduction or a loss of E-cadherin expression is a well-established hallmark of EMT. As a potent suppressor of E-cadherin, transcription factor ZEB1 is one of the key inducers of EMT, whose expression promotes tumorigenesis and metastasis of carcinomas. Bcl-2-associated athanogene 3 (BAG3) affects multifaceted cellular functions, including proliferation, apoptosis, cell adhesion and invasion, viral infection, and autophagy. Recently, we have reported a novel role of BAG3 implicated in EMT, while the mechanisms are poorly elucidated. The current study demonstrated that knockdown of BAG3 induced EMT, and increased cell migratory and invasiveness in thyroid cancer cells via transcriptional activation of ZEB1. We also found that BAG3 knockdown led to nuclear accumulation of β-catenin, which was responsible for the transcriptional activation of ZEB1. These results indicate BAG3 as a regulator of ZEB1 expression in EMT and as a regulator of metastasis in thyroid cancer cells, providing potential targets to prevent and/or treat thyroid cancer cell invasion and metastasis.

Knockdown of IQGAP1 inhibits proliferation and epithelial–mesenchymal transition by Wnt/β-catenin pathway in thyroid cancer

“…Therefore, better understanding of the molecular mechanisms of thyroid cancer metastasis is important for developing new medical treatments for thyroid cancer. The loss or reduction of the expression of E-cadherin, a cell adhesion molecule, is a crucial event in the initiation of EMT 23. In the current study, we also found that downregulation of IQGAP1 significantly augment epithelial marker E-cadherin expression.…”

“…The Wnt/β-catenin signaling pathway is involved in EMT in gastrulation, cardiac valve formation and cancer 27. Moreover, it has been showed that the activation of the Wnt/β-catenin pathway can promote EMT in various cancers 23. Therefore, to clarify how IQGAP1 regulated the EMT in thyroid cancer, we detected the expressions of β-catenin and downstream target genes (c-myc and cyclin D1) of the Wnt/β-catenin pathway, and our data presented that significant reductions in β-catenin, c-myc and cyclin D1 were observed in IQGAP1-knockdown thyroid cancer cells.…”

Human RNase L tunes gene expression by selectively destabilizing the microRNA-regulated transcriptome

“…The notion that RNase L shares common targets with these microRNAs suggests that RNase L may exhibit similar physiologic activities. To test whether RNase L regulates proliferation in HAP1 cells, we used a scratch wound healing assay, which has been used previously to evaluate the antiproliferative roles of miR-29 and miR-200 (31,42,44). We observed a rapid wound closure in RNase L-KO cells but not in WT cells, confirming a proliferation suppressor function of RNase L ( Fig.…”

BIS-mediated STAT3 stabilization regulates glioblastoma stem cell-like phenotypes

“…Additionally, Suzuki et al reported that BIS interacted with MMP-2 to positively regulate invasion by ovarian carcinoma cells [27]. Although there are discrepancies regarding the effect of BIS on EMT and/or metastasis [28, 29], BIS appears to play a key role in EMT and metastasis process. Considering that acquisition of EMT properties is closely related to CSC stemness [30–32], it is probable that BIS is involved in the regulation of CSC features, which is supported by the high expression of BIS in more aggressive tumors.…”