AI Article Synopsis
- Macrophages in breast tissue during obesity cause chronic inflammation, increasing the risk of breast cancer.
- Researchers found that exposing breast epithelial cells to macrophage-conditioned medium gives them cancer-like traits through the oncogene IKKε and changes in the serine biosynthesis pathway.
- An FDA-approved drug, amlexanox, shows promise in delaying tumor formation in obesity-related breast cancer models, indicating a potential new strategy to mitigate breast cancer risk linked to obesity and inflammation.
Article Abstract
During obesity, macrophages infiltrate the breast tissue leading to low-grade chronic inflammation, a factor considered responsible for the higher risk of breast cancer associated with obesity. Here, we formally demonstrate that breast epithelial cells acquire malignant properties when exposed to medium conditioned by macrophages derived from human healthy donors. These effects were mediated by the breast cancer oncogene IKKε and its downstream target-the serine biosynthesis pathway as demonstrated by genetic or pharmacological tools. Furthermore, amlexanox, an FDA-approved drug targeting IKKε and its homologue TBK1, delayed in vivo tumour formation in a combined genetic mouse model of breast cancer and high-fat diet-induced obesity/inflammation. Finally, in human breast cancer tissues, we validated the link between inflammation-IKKε and alteration of cellular metabolism. Altogether, we identified a pathway connecting obesity-driven inflammation to breast cancer and a potential therapeutic strategy to reduce the risk of breast cancer associated with obesity.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005540 | PMC |
| http://dx.doi.org/10.15252/emmm.201910491 | DOI Listing |
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