Growth of triple-negative breast cancer cells relies upon coordinate autocrine expression of the proinflammatory cytokines IL-6 and IL-8.
Triple-negative breast cancers (TNBC) are aggressive with no effective targeted therapies. A combined database analysis identified 32 inflammation-related genes differentially expressed in TNBCs and 10 proved critical for anchorage-independent growth. In TNBC cells, an LPA-LPAR2-EZH2 NF-κB signaling cascade was essential for expression of interleukin (IL)-6, IL-8, and CXCL1. Concurrent inhibition of IL-6 and IL-8 expression dramatically inhibited colony formation and cell survival in vitro and stanched tumor engraftment and growth in vivo. A Cox multivariable analysis of patient specimens revealed that IL-6 and IL-8 expression predicted patient survival times. Together these findings offer a rationale for dual inhibition of IL-6/IL-8 signaling as a therapeutic strategy to improve outcomes for patients with TNBCs.
Duke Scholars
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Related Subject Headings
- Triple Negative Breast Neoplasms
- Transfection
- Signal Transduction
- Proportional Hazards Models
- Oncology & Carcinogenesis
- Neoplastic Stem Cells
- Mice, Nude
- Mice
- Interleukin-8
- Interleukin-6
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Triple Negative Breast Neoplasms
- Transfection
- Signal Transduction
- Proportional Hazards Models
- Oncology & Carcinogenesis
- Neoplastic Stem Cells
- Mice, Nude
- Mice
- Interleukin-8
- Interleukin-6