| First Author | Zhu B | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 29 | Pages | 20102-19 |
| PubMed ID | 24898257 | Mgi Jnum | J:216623 |
| Mgi Id | MGI:5609107 | Doi | 10.1074/jbc.M114.551069 |
| Citation | Zhu B, et al. (2014) The nuclear receptor peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) promotes oncogene-induced cellular senescence through repression of endoplasmic reticulum stress. J Biol Chem 289(29):20102-19 |
| abstractText | Endoplasmic reticulum (ER) stress and ER stress-associated unfolded protein response (UPR) can promote cancer cell survival, but it remains unclear whether they can influence oncogene-induced senescence. The present study examined the role of ER stress in senescence using oncogene-dependent models. Increased ER stress attenuated senescence in part by up-regulating phosphorylated protein kinase B (p-AKT) and decreasing phosphorylated extracellular signal-regulated kinase (p-ERK). A positive feed forward loop between p-AKT, ER stress, and UPR was discovered whereby a transient increase of ER stress caused reduced senescence and promotion of tumorigenesis. Decreased ER stress was further correlated with increased senescence in both mouse and human tumors. Interestingly, H-RAS-expressing Pparbeta/delta null cells and tumors having increased cell proliferation exhibited enhanced ER stress, decreased cellular senescence, and/or enhanced tumorigenicity. Collectively, these results demonstrate a new role for ER stress and UPR that attenuates H-RAS-induced senescence and suggest that PPARbeta/delta can repress this oncogene-induced ER stress to promote senescence in accordance with its role as a tumor modifier that suppresses carcinogenesis. |
