MED28 Regulates Epithelial-Mesenchymal Transition Through NFκB in Human Breast Cancer Cells.
MED28, a mammalian Mediator subunit, was found highly expressed in several types of malignancy, including breast cancer. Recently, we have identified a role of MED28 in regulating both cell growth and migration in human breast cancer cells. In epithelium-derived solid tumor, migration and invasion are preceded by the progression of epithelial-mesenchymal transition (EMT) which calls for downregulation of epithelial markers as well as upregulation of mesenchymal markers, among other features. The objective of this study was to investigate a putative role of MED28 in the progression of EMT in human breast cancer cells. In fibroblast-like MDA-MB-231 cells, suppression of MED28 attenuated the mesenchymal morphology, concomitantly with a reduction of several mesenchymal biomarkers and Snail, a transcriptional repressor of E-cadherin. The suppression effect was also accompanied by downregulation of p-NFκB/p65. However, overexpression of MED28 exhibited in an opposite manner. In epithelial MCF7 cells, administration of Adriamycin®, an experimental EMT induction system, led to a mesenchyme-like appearance correlated with increased expression of MED28, p-p65, and Snail, and a reciprocal change of epithelial and mesenchymal markers. Furthermore, suppression of MED28 attenuated the experimental EMT effect and restored the original expression status of E-cadherin and MMP9 in MCF7 cells. Our data indicate that MED28 modulates the development of EMT through NFκB in human breast cancer cells, further reinforcing the significance of MED28 in the progression of breast cancer on top of its role in cell growth and migration. J. Cell. Physiol. 232: 1337-1345, 2017. © 2016 Wiley Periodicals, Inc.
Department of Nutrition, China Medical University, Taichung, Taiwan, R.O.C.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan, R.O.C.
Chun-Yin
CY
Huang
Department of Nutrition, China Medical University, Taichung, Taiwan, R.O.C.
Nien-Tsu
NT
Hsieh
Department of Nutrition and Health Sciences, Chang Jung Christian University, Tainan, Taiwan, R.O.C.
Chun-I
CI
Li
Department of Nutrition and Health Sciences, Chang Jung Christian University, Tainan, Taiwan, R.O.C.
Yu-Ting
YT
Weng
Department of Microbiology and Immunology, National Cheng Kung University, Tainan, Taiwan, R.O.C.
Hsiao-Sheng
HS
Liu
Department of Nutrition and Health Sciences, Chang Jung Christian University, Tainan, Taiwan, R.O.C.
Ming-Fen
MF
Lee
D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D006801:Humans; D056892:Mediator Complex / Q000378:metabolism*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects; D000071250:Snail Family Transcription Factors / Q000378:metabolism
D014408:Biomarkers, Tumor; C496877:MED28 protein, human; D056892:Mediator Complex; D016328:NF-kappa B; D000071250:Snail Family Transcription Factors; D004317:Doxorubicin