| RRC ID |
87358
|
| 著者 |
Matsumoto A, Inoko A, Tanaka T, Konishi GI, Hosoda W, Kojima T, Ohnishi K, Ikenouchi J.
|
| タイトル |
Chemotherapy resistance due to epithelial-to-mesenchymal transition is caused by abnormal lipid metabolic balance.
|
| ジャーナル |
Elife
|
| Abstract |
Invasive cancer is defined by the loss of epithelial cell traits resulting from the ectopic expression of epithelial-mesenchymal transition (EMT)-related transcription factors such as Snail. Although EMT is known to impart chemoresistance to cancer cells, the precise molecular mechanisms remain elusive. We found that Snail expression confers chemoresistance by upregulating the cholesterol efflux pump ABCA1 as a countermeasure to the excess of cytotoxic free cholesterol relative to its major interaction partner in cellular membranes, sphingomyelin. This imbalance is introduced by the transcriptional repression of enzymes involved in the biosynthesis of sphingomyelin by Snail. Inhibiting esterification of cholesterol, which renders it inert, selectively suppresses growth of a xenograft model of Snail-positive kidney cancer. Our findings offer a new perspective on lipid-targeting strategies for invasive cancer therapy.
|
| 巻・号 |
13
|
| 公開日 |
2026-1-12
|
| DOI |
10.7554/eLife.104374
|
| PII |
104374
|
| PMID |
41521893
|
| PMC |
PMC12795503
|
| MeSH |
ATP Binding Cassette Transporter 1 / genetics
ATP Binding Cassette Transporter 1 / metabolism
Animals
Antineoplastic Agents / pharmacology
Cell Line, Tumor
Cholesterol / metabolism
Drug Resistance, Neoplasm*
Epithelial-Mesenchymal Transition*
Humans
Kidney Neoplasms / drug therapy
Lipid Metabolism*
Mice
Snail Family Transcription Factors / genetics
Snail Family Transcription Factors / metabolism
Sphingomyelins / metabolism
|
| リソース情報 |
| ヒト・動物細胞 |
TUHR14TKB(RCB1383) |
