Reference - Detail
| RRC ID | 36023 |
|---|---|
| Author | Natarajan B, Gaur R, Hemmingsson O, Kao G, Naredi P. |
| Title | Depletion of the ER chaperone ENPL-1 sensitizes C. elegans to the anticancer drug cisplatin. |
| Journal | Worm |
| Abstract |
Cisplatin is an essential chemotherapeutic drug in the treatment of many cancers. Its use, however, is limited by the development of resistance in many tumors. The ability to re-sensitize resistant tumors could significantly strengthen cisplatin therapy in patients. Caenorhabditis elegans is a suitable model for studying the cytoplasmic role of cisplatin in tumor cells. We have previously shown that the ATPase ASNA-1 has similar roles as a factor governing cisplatin sensitivity in mammalian tumor cells and C. elegans. Here we study the endoplasmic reticulum (ER) resident chaperone ENPL-1/GRP94 and find that its depletion makes worms sensitive to cisplatin. Elevated ER stress levels in enpl-1 mutants is the likely cause of this sensitivity because a correlation can be made between cisplatin sensitivity and the high ER stress levels. We also find that asna-1 mutants have elevated unfolded protein response (UPR) activity and that the intrinsically cisplatin resistant wild-type worms become sensitive when ER stress is high. We conclude that enpl-1 is a cisplatin sensitizing factor and suggest that manipulation of its levels or of UPR activity will enhance the effects of cisplatin based cancer therapy. |
| Volume | 2(1) |
| Pages | e24059 |
| Published | 2013-1-1 |
| DOI | 10.4161/worm.24059 |
| PII | 2012WORM085RR |
| PMID | 24058864 |
| PMC | PMC3670465 |
| Altmetric score |
オルトメトリクス指標項目
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| Total number of mentions | 0 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm3738 |