PPAR-delta promotes survival of breast cancer cells in harsh metabolic conditions
| Autor: | Sun L, Yonghong Shi, Wang X, Xu Z, Gorczynski R, You-Jun Li, Wang G, Spaner De |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Cancer Biology medicine.disease medicine.disease_cause Molecular oncology 3. Good health Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Breast cancer Growth factor receptor Downregulation and upregulation 030220 oncology & carcinogenesis Cancer cell medicine Cancer research Peroxisome proliferator-activated receptor delta Original Article Carcinogenesis Molecular Biology |
| Zdroj: | Oncogenesis |
| ISSN: | 2157-9024 |
| Popis: | Expression of the nuclear receptor peroxisome proliferator activated receptor delta (PPARδ) in breast cancer cells is negatively associated with patient survival, but the underlying mechanisms are not clear. High PPARδ protein levels in rat breast adenocarcinomas were found to be associated with increased growth in soft agar and mice. Transgenic expression of PPARδ increased the ability of human breast cancer cell lines to migrate in vitro and form lung metastases in mice. PPARδ also conferred the ability to grow in exhausted tissue culture media and survive in low-glucose and other endoplasmic reticulum stress conditions such as hypoxia. Upregulation of PPARδ by glucocorticoids or synthetic agonists also protected human breast cancer cells from low glucose. Survival in low glucose was related to increased antioxidant defenses mediated in part by catalase and also to late AKT phosphorylation, which is associated with the prolonged glucose-deprivation response. Synthetic antagonists reversed the survival benefits conferred by PPARδ in vitro. These findings suggest that PPARδ conditions breast cancer cells to survive in harsh microenvironmental conditions by reducing oxidative stress and enhancing survival signaling responses. Drugs that target PPARδ may have a role in the treatment of breast cancer. |
| Databáze: | OpenAIRE |
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