2026-01-30 九州大学
図 浸潤がん細胞(TE-8)はコレステロール排出トランスポーターABCA1を高発現することで化学治療抵抗性を獲得する
<関連情報>
- https://www.kyushu-u.ac.jp/ja/researches/view/1406
- https://www.kyushu-u.ac.jp/f/64636/26_0129_03.pdf
- https://elifesciences.org/articles/104374
上皮間葉転換による化学療法耐性は脂質代謝バランスの異常によって引き起こされる Chemotherapy resistance due to epithelial-to-mesenchymal transition is caused by abnormal lipid metabolic balance
Atsushi Matsumoto,Akihito Inoko,Takuya Tanaka,Gen-Ichi Konishi,Waki Hosoda,Takahiro Kojima,Koji Ohnishi,Junichi Ikenouchi,
eLife Published:Jan 12, 2026
DOI:https://doi.org/10.7554/eLife.104374.3
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.
