Journal
ONCOTARGET
Volume 6, Issue 28, Pages 25320-25338Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4659
Keywords
connective tissue growth factor (CTGF); epithelial-mesenchymal transition (EMT); collagen I fibers; tumor necrosis factor receptor 1 (TNFR1) pathway; breast cancer
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Funding
- NIH [U54 CA149196]
- John S. Dunn Research Foundation
- Keck Center for Interdisciplinary Bioscience Training of the Gulf Coast Consortia (CPRIT) [RP140113]
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Interactions among tumor cells, stromal cells, and extracellular matrix compositions are mediated through cytokines during tumor progression. Our analysis of 132 known cytokines and growth factors in published clinical breast cohorts and our 84 patient-derived xenograft models revealed that the elevated connective tissue growth factor (CTGF) in tumor epithelial cells significantly correlated with poor clinical prognosis and outcomes. CTGF was able to induce tumor cell epithelial-mesenchymal transition (EMT), and promote stroma deposition of collagen I fibers to stimulate tumor growth and metastasis. This process was mediated through CTGF-tumor necrosis factor receptor I (TNFR1)-I kappa B autocrine signaling. Drug treatments targeting CTGF, TNFR1, and I kappa B signaling each prohibited the EMT and tumor progression.
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