Cyclin D1b Splice Variant Promotes αvβ3-mediated EMT Induced by LPS in Breast Cancer Cells
10.1007/s11596-018-1902-5
- Author:
Bao-Ping LUO
1
;
Jing LUO
;
Yi-Bing HU
;
Xiao-Wei YAO
;
Feng-Hua WU
Author Information
1. Department of Tumor
- Keywords:
cyclin D1b;
epithelial-to-mesenchymal transition;
lipopolysaccharide;
αvβ3-integrin;
breast cancer
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2018;38(3):467-472
- CountryChina
- Language:Chinese
-
Abstract:
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 D 1 b.However,the role of cyclin D1b in LPS-induced EMT has not been fully elucidated.In the present study,we described that cyclin D1b augmented EMT induced by LPS in MCF-7 breast cancer cells.Cyclin D1b markedly amplified integrin αvβ3 expression,which was further up-regulated under LPS stimulation.Our results showed ectopic expression of cyclin D1b promoted invasiveness of epithelial-like MCF-7 cells under LPS stimulation.Additionally,LPS-induced metastasis and EMT in MCF-7-D1b cells might depend on αvβ3 expression.Further exploration indicated that cyclin D1b 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 D1b.Specifically,all these effects were in a cyclin D1a independent manner.Taken all together,LPS up-regulated integrin αvβ3 expression in MCF-7 cells with high expression of cyclin D 1b and induced EMT in breast cancer cells,which highlights that cyclin D1b may act as an endogenous pathway participating in exogenous signal inducing EMT in breast cancer cells.
