Stabilization of C/EBPβ through direct interaction with STAT3 in H-Ras transformed human mammary epithelial cells.

Abstract

Signal transducer and activator of transcription 3 (STAT3) plays important roles in cancer-associated inflammation by controlling expression of proinflammatory cytokines and chemokines. Recent studies suggest that C/EBPβ (CCAAT-enhancer binding protein beta) and STAT3 synergistically stimulate cancer cell proliferation and epithelial-mesenchymal transition. C/EBPβ is a leucine-zipper transcription factor that regulates expression of a variety of inflammatory cytokines or chemokines, such as IL-8, G-CSF (granulocyte colony stimulating factor), and GM-CSF (granulocyte macrophage colony stimulating factor) which induce neutrophil infiltration and differentiation. However, molecular mechanisms by which STAT3 and C/EBPβ cooperatively interact had not been fully elucidated. In this study, we found that the level of C/EBPβ protein, but not that of its mRNA transcript, was decreased in the absence of STAT3 in H-Ras transformed human mammary epithelial (H-Ras MCF10A) cells. In addition, silencing STAT3 dramatically induced ubiquitination of C/EBPβ for proteasomal degradation. Furthermore, direct interaction between STAT3 and C/EBPβ was confirmed by immunoprecipitation and proximity ligation assays. Taken together, these results suggest that STAT3 stabilizes C/EBPβ, thereby promoting cancer-associated inflammation.

• Authors: Lil-Li Lee, Su-Jung Kim, Young-Il Hahn, Jeong-Hoon Jang, Soma Saeidi, Young-Joon Surh
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 546 Pg. 130-137 (03 26 2021) ISSN: 1090-2104 [Electronic] United States
• PMID: 33582555 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• CCAAT-Enhancer-Binding Protein-beta
• CEBPB protein, human
• Interleukin-8
• STAT3 Transcription Factor
• STAT3 protein, human
• Granulocyte Colony-Stimulating Factor
• Granulocyte-Macrophage Colony-Stimulating Factor
• Proteasome Endopeptidase Complex

Topics

• Breast (pathology)
• Breast Neoplasms (metabolism, pathology)
• CCAAT-Enhancer-Binding Protein-beta (antagonists & inhibitors, metabolism)
• Cell Line, Transformed
• Cell Transformation, Neoplastic
• Epithelial Cells (pathology)
• Feedback, Physiological
• Female
• Genes, ras
• Granulocyte Colony-Stimulating Factor (metabolism)
• Granulocyte-Macrophage Colony-Stimulating Factor (metabolism)
• Humans
• Inflammation (metabolism, pathology)
• Interleukin-8 (metabolism)
• Neutrophils (cytology)
• Proteasome Endopeptidase Complex (metabolism)
• Protein Binding
• Protein Stability
• STAT3 Transcription Factor (metabolism)
• Signal Transduction
• Ubiquitination