Targeting the IL-1R/MyD88 Signaling Axis: Unraveling Inflammatory Mediators Driving Breast Cancer Progression and Therapy Resistance
Keywords:
Breast cancer, IL-1R/MyD88 axis, IRAK1, TRAF6, NF-κB, MAPK, Inflammation, Therapeutic resistance, Tumor progression, MCF7 cellsAbstract
Breast cancer is the second leading cause of cancer-related death among women, with treatment efficacy hindered by the heterogeneity of the disease. Understanding the molecular signaling pathways that govern tumor progression and therapy resistance is essential for improving clinical outcomes. One critical pathway is the IL-1 receptor (IL-1R)/MyD88 axis, which regulates immune responses and inflammation. In this study, we investigated the role of key inflammatory mediators, including IRAK1, TRAF6, NF-κB, p38MAPK, and JNK, in the progression of breast cancer. We compared the expression of these molecules in MCF7 breast cancer cells and normal human primary dermal fibroblasts (HPDF) at 24- and 72-hour time points. Our results demonstrate significantly higher expression levels of IRAK1, TRAF6, NF-κB, p38MAPK, and JNK in MCF7 cells compared to HPDF cells. These findings highlight the contribution of MyD88-mediated inflammatory signaling to breast cancer cell proliferation, survival, and resistance to apoptosis. Additionally, elevated expression of these signaling components was associated with increased activation of pro-inflammatory and pro-survival pathways, suggesting that they play a key role in tumorigenesis and therapy resistance. This study provides valuable insights into the molecular mechanisms underlying breast cancer progression and emphasizes the potential of targeting the IL-1R/MyD88 signaling pathway for therapeutic intervention, particularly in breast cancer subtypes where these pathways are dysregulated.
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