Activation of β-catenin signaling is critical for doxorubicin-induced epithelial–mesenchymal transition in BGC-823 gastric cancer cell line

Abstract

The epithelial-mesenchymal transition (EMT) is a fundamental process governing morphogenesis in multicellular organisms and has recently been implicated in promoting carcinoma invasion and metastasis. Besides their therapeutic effects, accumulating evidences suggest that chemotherapeutic agents also induced EMT and enhanced the malignancy of treated cancer cells; however, the mechanism(s) still remains unclear. Here, we investigated the role of β-catenin signaling in doxorubicin (Dox)-induced EMT in human gastric cancer cell line BGC-823. We found that the transient treatment of Dox induced EMT and enhanced the in vitro migration ability of cancer cells. We also found that β-catenin signaling was activated upon Dox treatment. Inhibition of β-catenin by indomethacin (Indo) or siRNA suppressed Dox-induced EMT and decreased cancer cell migration ability. Our results showed that β-catenin signaling was critical to Dox-induced EMT. Indo and other β-catenin inhibitors may have a potential implication in prevention of gastric cancer metastasis.

An Epigenetic Mechanism Underlying Doxorubicin Induced EMT in the Human BGC-823 Gastric Cancer Cell

“…These data indicated that the EMT phenotype was inherited in ltDSCs. We previous reported that β-catenin signaling was activated after 48 h Dox treatment (Han et al, 2013). Here we also found that the mRNA level of β-catenin was higher in ltDSCs than parental cells (Figure 2a), suggesting the sustained activation of β-catenin signaling in ltDSCs.…”

“…These long term cultured DSC still exhibited a typical mesenchymal morphology and expressed high levels of mesenchymal cell markers and chromatin reprogramming factors. Our previous study showed that 48 h Dox treatment could induced EMT in BGC-823 cells (Han et al, 2013), which precluded the possibility that the EMT phenotype of ltDSCs was caused by DNA mutation in such short time of drug exposure. Together, our data suggested that an epigenetic mechanism was involved in the maintenance of EMT in ltDSCs.…”

“…We showed that the high level of Vimentin in ltDSCs was sensitive to p300 knockdown, indicating that histone acetylation played a role in the maintenance of EMT in ltDSCs, although the details need further investigation. We previously identified the critical role of β-catenin signaling in Dox induced EMT in BGC-823 cells (Han et al, 2013). Here we found that β-catenin signaling was continuously activated in ltDSCs.…”

“…We previously reported that transient (48 h) treatment of anti-cancer drug doxorubicin (Dox) could induce EMT in human gastric cancer BGC-823 cells (Han et al, 2013). However, the long term effects of this transient drug treatment were unknown.…”

Interaction between Wnt/β-catenin pathway and microRNAs regulates epithelial-mesenchymal transition in gastric cancer (Review)

“…Qu et al (100) reported that overexpressed sFRP1 is correlated with EMT induction in GC cells as well as lymph node migration and reduced survival time. Han et al (101) established an EMT model by treating BGC-823 cells with doxorubicin and elaborated upregulation of β-catenin, LEF1, c-Myc which indicates activated β-catenin signaling. Thereafter, noticeable reversion of EMT biomarkers was found when applying indomethacin or siRNA to stamp down β-catenin.…”