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MED28 Regulates Proinflammatory Cytokine‐induced Epithelial–Mesenchymal Transition and Invasion in Human Breast Cancer Cells
Author(s) -
Hsieh NienTsu,
Huang ChunYin,
Li ChunI,
Weng YuTing,
Lee MingFen
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.809.16
Subject(s) - proinflammatory cytokine , epithelial–mesenchymal transition , cancer research , carcinogenesis , tumor necrosis factor alpha , cytokine , biology , mesenchymal stem cell , breast cancer , cancer , immunology , inflammation , metastasis , microbiology and biotechnology , genetics
MED28, one of the Mediator subunits, exhibits multiple cellular roles, including involved in transcriptional activation and as a merlin, Grb2, and cytoskeleton‐associated protein, which is highly expressed in several types of malignancy including breast and colorectal tumors. Chronic inflammation, as suggested as one of the hallmarks of cancer, may promote carcinogenesis. Inflammatory cytokines such as tumor necrosis factor‐alpha (TNFα) may mediate tumor initiation, promotion, and progression. Recently, we have identified that MED28 is involved in regulating cell growth, epithelial–mesenchymal transition (EMT), and migration in human breast cancer cells. The objective of this study is to investigate if MED28 is involved in the proinflammatory cytokine‐induced EMT in human breast cancer cells. In aggressive MDA‐MB‐231 cells, MED28 suppression attenuated the mesenchymal morphology and reduced the expression of several mesenchymal biomarkers; however, MED28 overexpression exhibited a reciprocal effect. In addition, TNFα upregulated the expression of the target genes of NFκB/p65 and enhanced an even more aggressive phenotype, whereas suppression of MED28 attenuated the effect. Moreover, pterostilbene, a resveratrol analogue, suppressed the expression of MED28, p‐p65, and p65 downstream target genes, which warrants further investigation for a putative translational application in breast cancer. Support or Funding Information This work was supported by the grants NSC102‐2320‐B‐309‐001‐MY3 and MOST105‐2320‐B‐309‐001 to M‐F Lee and MOST103‐2815‐C‐309‐012‐B to C‐I Li.