Epithelial-to-mesenchymal transition （EMT） plays a critical role in cancer metastasis, and is relevant to the inflammatory microenvironment. Lipopolysaccharide （LPS）, a cell wall constituent of gram-negative bacte...Epithelial-to-mesenchymal transition （EMT） plays a critical role in cancer metastasis, and is relevant to the inflammatory microenvironment. Lipopolysaccharide （LPS）, a cell wall constituent of gram-negative bacteria, has been reported to induce EMT of cancer cells through TLR4 signal. We previously reported that LPS promoted metastasis of mesenchymallike breast cancer cells with high expression of cyclin Dlb. However, the role of cyclin Dlb in LPS-induced EMT has not been fully elucidated. In the present study, we described that cyclin Dlb augmented EMT induced by LPS in MCF-7 breast cancer cells. Cyclin Dlb markedly amplified integrin αvβ3 expression, which was further up-regulated under LPS stimulation. Our results showed ectopic expression of cyclin Dlb promoted invasiveness of epithelial-like MCF-7 cells under LPS stimulation. Additionally, LPS-induced metastasis and EMT in MCF- 7-Dlb cells might depend on αvβ3 expression. Further exploration indicated that cyclin Dlb cooperated with HoxD3, a transcription factor promoting αvβ3 expression, to promote LPS- induced EMT. Knockout of HoxD3 repressed LPS-induced EMT and αvβ3 over-expression in MCF-7 cells with high expression of cyclin Dlb. Specifically, all these effects were in a cyclin Dla independent manner. Taken all together, LPS up-regulated integrin αvβ3 expression in MCF-7 cells with high expression of cyclin D lb and induced EMT in breast cancer cells, which highlights that cyclin Dlb may act as an endogenous pathway participating in exogenous signal inducing EMT in breast cancer cells.展开更多
基金This study was supported by National Natural Science Foundation of China （No. 81702920） and China Postdoctoral Science Foundation （Nos. 2016M602311, 2016T90693, 2015M570642）.
文摘Epithelial-to-mesenchymal transition （EMT） plays a critical role in cancer metastasis, and is relevant to the inflammatory microenvironment. Lipopolysaccharide （LPS）, a cell wall constituent of gram-negative bacteria, has been reported to induce EMT of cancer cells through TLR4 signal. We previously reported that LPS promoted metastasis of mesenchymallike breast cancer cells with high expression of cyclin Dlb. However, the role of cyclin Dlb in LPS-induced EMT has not been fully elucidated. In the present study, we described that cyclin Dlb augmented EMT induced by LPS in MCF-7 breast cancer cells. Cyclin Dlb markedly amplified integrin αvβ3 expression, which was further up-regulated under LPS stimulation. Our results showed ectopic expression of cyclin Dlb promoted invasiveness of epithelial-like MCF-7 cells under LPS stimulation. Additionally, LPS-induced metastasis and EMT in MCF- 7-Dlb cells might depend on αvβ3 expression. Further exploration indicated that cyclin Dlb cooperated with HoxD3, a transcription factor promoting αvβ3 expression, to promote LPS- induced EMT. Knockout of HoxD3 repressed LPS-induced EMT and αvβ3 over-expression in MCF-7 cells with high expression of cyclin Dlb. Specifically, all these effects were in a cyclin Dla independent manner. Taken all together, LPS up-regulated integrin αvβ3 expression in MCF-7 cells with high expression of cyclin D lb and induced EMT in breast cancer cells, which highlights that cyclin Dlb may act as an endogenous pathway participating in exogenous signal inducing EMT in breast cancer cells.
