Interleukin-6 induces an epithelial–mesenchymal transition phenotype in human breast cancer cells

By N. Sullivan, A. Sasser, A. Axel, F. Vesuna, V. Raman, N. Ramirez, T. Oberyszyn, Brett Hall. Oncogene, 2009

755 citations recorded by the source corpus.

Breast tumor interleukin-6 (IL-6) levels increase with tumor grade, and elevated serum IL-6 correlates with poor breast cancer patient survival. Epithelial–mesenchymal transition (EMT) phenotypes such as impaired E-cadherin expression or aberrant Vimentin induction are associated with enhanced metastasis and unfavorable clinical outcome in breast cancer. Despite this fact, few tumor microenvironment-derived extracellular signaling factors capable of provoking such a phenotypic transition have been identified. In this study, we showed that IL-6 promoted E-cadherin repression among a panel of estrogen receptor-α-positive human breast cancer cells. Furthermore, ectopic stable IL-6 expressing MCF-7 breast adenocarcinoma cells (MCF-7IL−6) exhibited an EMT phenotype characterized by impaired E-cadherin expression and induction of Vimentin, N-cadherin, Snail and Twist. MCF-7IL−6 cells formed xenograft tumors that displayed loss of E-cadherin, robust Vimentin induction, increased proliferative indices, advanced tumor grade and undifferentiated histology. Finally, we showed aberrant IL-6 production and STAT3 activation in MCF-7 cells that constitutively express Twist, a metastatic regulator and direct transcriptional repressor of E-cadherin. To our knowledge, this is the first study that shows IL-6 as an inducer of an EMT phenotype in breast cancer cells and implicates its potential to promote breast cancer metastasis.

Subfields: Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/68c5963d884b11c3c3030487a203af814bfcad42

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Oncology

1. M. Nieto
2. J. P. Thiery
3. Thomas Brabletz
4. Simone Brabletz
5. R. Weinberg
6. R. Huang
7. H. Acloque
8. T. Hirano

In Pulmonary and Respiratory Medicine

1. J. P. Thiery
2. M. Nieto
3. Thomas Brabletz
4. R. Huang
5. R. Weinberg
6. Jormay Lim

Citations in the corpus

• Epithelial-mesenchymal transitions in development and disease. (2009, background): “(IL-6) also promotes EMT in breast cancer cells, and Snail can induce IL-6 expression (Lyons et al., 2008; Sullivan et al., 2009),”
• IL-6 in inflammation, autoimmunity and cancer (2020, background): “IL-6–STAT3 signaling in adipocytes is known to be involved in adipocyte-induced EMT in breast cancer cells (23) and obesity-promoted HCC (258).”
• Dynamic EMT: a multi‐tool for tumor progression (2021, positive): “…and promote stemness, invasion and regulation of genes involved in EMT mediated by SNAIL, TWIST and ZEB 1 as demonstrated in colon, breast and renal cell carcinoma (Bates & Mercurio, 2003 ; Sullivan et al , 2009 ; Ho et al , 2012 ; Li et al , 2012 ; Miao et al , 2014 ; Ieda et al , 2019 ).”
• Crosstalk between cancer cells and tumor associated macrophages is required for mesenchymal circulating tumor cell-mediated colorectal cancer metastasis (2019, background): “As a key cytokine linked to inflammation-associated cancer, IL6 is implicated in the facilitation of angiogenesis, tumorigenesis and progression by complicated mechanisms, such as increasing expression of invasion-related genes (Twist and MMP-1) and anti-apoptotic factors (Bcl-2 and Bcl-xL), and act”