論文 - 詳細
| RRC ID | 54810 |
|---|---|
| 著者 | Mahoney CE, Pirman D, Chubukov V, Sleger T, Hayes S, Fan ZP, Allen EL, Chen Y, Huang L, Liu M, Zhang Y, McDonald G, Narayanaswamy R, Choe S, Chen Y, Gross S, Cianchetta G, Padyana AK, Murray S, Liu W, Marks KM, Murtie J, Dorsch M, Jin S, Nagaraja N, Biller SA, Roddy T, Popovici-Muller J, Smolen GA. |
| タイトル | A chemical biology screen identifies a vulnerability of neuroendocrine cancer cells to SQLE inhibition. |
| ジャーナル | Nat Commun |
| Abstract |
Aberrant metabolism of cancer cells is well appreciated, but the identification of cancer subsets with specific metabolic vulnerabilities remains challenging. We conducted a chemical biology screen and identified a subset of neuroendocrine tumors displaying a striking pattern of sensitivity to inhibition of the cholesterol biosynthetic pathway enzyme squalene epoxidase (SQLE). Using a variety of orthogonal approaches, we demonstrate that sensitivity to SQLE inhibition results not from cholesterol biosynthesis pathway inhibition, but rather surprisingly from the specific and toxic accumulation of the SQLE substrate, squalene. These findings highlight SQLE as a potential therapeutic target in a subset of neuroendocrine tumors, particularly small cell lung cancers. |
| 巻・号 | 10(1) |
| ページ | 96 |
| 公開日 | 2019-1-9 |
| DOI | 10.1038/s41467-018-07959-4 |
| PII | 10.1038/s41467-018-07959-4 |
| PMID | 30626880 |
| PMC | PMC6327044 |
| MeSH | Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Cell Line, Tumor Cholesterol / biosynthesis Drug Delivery Systems* Drug Screening Assays, Antitumor* Gene Deletion Gene Expression Regulation, Enzymologic / drug effects Gene Expression Regulation, Neoplastic / drug effects Humans Squalene Monooxygenase / antagonists & inhibitors* Squalene Monooxygenase / metabolism* |
| IF | 11.878 |
| 引用数 | 1 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 14 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Lu-139(RCB0469) |