論文 - 詳細
| RRC ID | 72357 |
|---|---|
| 著者 | Yano H, Fujiwara Y, Horlad H, Pan C, Kai K, Niino D, Ohsawa K, Higashi M, Nosaka K, Okuno Y, Tamaru JI, Mukasa A, Matsuoka M, Komohara Y. |
| タイトル | Blocking cholesterol efflux mechanism is a potential target for antilymphoma therapy. |
| ジャーナル | Cancer Sci |
| Abstract |
Cholesterol is an essential plasma membrane lipid for the maintenance of cellular homeostasis and cancer cell proliferation. Free cholesterol is harmful to cells; therefore, excessive free cholesterol must be quickly esterified by acetyl-coenzyme A:cholesterol acetyltransferase (ACAT) and exported by scavenger receptor class B member I (SR-BI) or ATP-binding cassette protein A1 from specific cells such as macrophage foam cells, which contain cholesteryl ester-derived vacuoles. Many vacuoles are present in the cytoplasm of Burkitt lymphoma cells. In this study, we observed that these vacuoles are often seen in high-grade lymphomas. Cell culture study using lymphoma cell lines found that esterified cholesterol is the main component of these vacuoles and the expression of cholesterol metabolism-related molecules was significantly upregulated in lymphoma cell lines, with SR-BI and ACAT inhibitors (BLT-1 and CI-976, respectively) impeding lymphoma cell proliferation. Cytoplasmic free cholesterol was increased by ACAT and SR-BI inhibitors, and the accumulation of free cholesterol induced lymphoma cell apoptosis by inducing endoplasmic reticulum stress. Furthermore, synergistic effects of SR-BI and ACAT inhibitors were observed in a preclinical study. Treatment with SR-BI inhibitor suppressed lymphoma progression in a tumor-bearing mouse model, whereas ACAT inhibitor did not. Therefore, SR-BI inhibitors are potential new antilymphoma therapeutics that target cholesterol metabolism. |
| 巻・号 | 113(6) |
| ページ | 2129-2143 |
| 公開日 | 2022-6-1 |
| DOI | 10.1111/cas.15349 |
| PMID | 35343027 |
| PMC | PMC9207360 |
| MeSH | ATP-Binding Cassette Transporters* / metabolism Animals Cholesterol / metabolism Cholesterol Esters / metabolism Foam Cells* / metabolism Foam Cells* / pathology Humans Mice Scavenger Receptors, Class B / metabolism |
| IF | 4.966 |
| 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 | 3 |
| 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 | ATN-1)RCB1440) 103-LCL(RCB2082) 141‐LCL(RCB2083) DAUDI(RCB1640) BALL-1(RCB1882) TL-1(RCB1871) RAJI(RCB1647) SLVL(RCB1702) HKBML(RCB0820) |