Metabolic enzyme ACSL3 is a prognostic biomarker and correlates with anticancer effectiveness of statins in non-small cell lung cancer.
Metabolic enzyme ACSL3 is a prognostic biomarker and correlates with anticancer effectiveness of statins in non-small cell lung cancer.
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DOI：
10.1002/1878-0261.12816
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发表时间：
2020-12
影响因子：
6.6
通讯作者：
Ramírez de Molina A
中科院分区：
文献类型：
--
作者：
Fernández LP;Merino M;Colmenarejo G;Moreno-Rubio J;Sánchez-Martínez R;Quijada-Freire A;Gómez de Cedrón M;Reglero G;Casado E;Sereno M;Ramírez de Molina A
ACSL3酶的过表达是非小细胞肺癌（NSCLC）的不利预后标志物。此外，ACSL 3的过表达增加了细胞增殖、迁移和侵袭，改变了癌细胞的代谢特性。他汀类药物给药可产生抗增殖作用，重要的是，他汀类药物治疗后ACSL 3高表达水平的患者比未接受他汀类药物治疗的患者预后更好。 肺癌是最常见的癌症之一，仍然以高死亡率为特征。由于脂质代谢有助于癌症代谢重编程，因此几种脂质代谢基因被认为是癌症的预后生物标志物。他汀类药物是一类用于治疗心血管疾病的降脂化合物，目前正在研究其抗肿瘤作用。然而，其确切的作用机制和具体的条件下，他们应该管理仍然不清楚。在这里，我们发现辛伐他汀治疗有效地促进了非小细胞肺癌（NSCLC）细胞中的抗增殖作用并调节了脂质代谢相关途径，并且他汀类药物的抗增殖作用通过酰基辅酶A合成酶长链家族成员3（ACSL 3）的过表达而增强。此外，ACSL3过表达与高级别NSCLC患者的临床结局较差相关。最后，我们发现ACSL3高表达水平的患者显示出他汀类药物治疗的临床获益。因此，我们的研究强调ACSL 3作为NSCLC的预后生物标志物，可用于选择从他汀类药物给药中获得临床获益的患者。
Overexpression of the enzyme ACSL3 is an unfavorable prognostic marker in non‐small cell lung cancer (NSCLC). Moreover, overexpression of ACSL3 increases cell proliferation, migration, and invasion, altering the metabolic properties of cancer cells. Administration of statins causes antiproliferative effects and, importantly, patients with high expression levels of ACSL3 following statin treatment display better prognosis than those not treated with statins. Lung cancer is one of the most common cancers, still characterized by high mortality rates. As lipid metabolism contributes to cancer metabolic reprogramming, several lipid metabolism genes are considered prognostic biomarkers of cancer. Statins are a class of lipid‐lowering compounds used in treatment of cardiovascular disease that are currently studied for their antitumor effects. However, their exact mechanism of action and specific conditions in which they should be administered remains unclear. Here, we found that simvastatin treatment effectively promoted antiproliferative effects and modulated lipid metabolism‐related pathways in non‐small cell lung cancer (NSCLC) cells and that the antiproliferative effects of statins were potentiated by overexpression of acyl‐CoA synthetase long‐chain family member 3 (ACSL3). Moreover, ACSL3 overexpression was associated with worse clinical outcome in patients with high‐grade NSCLC. Finally, we found that patients with high expression levels of ACSL3 displayed a clinical benefit of statins treatment. Therefore, our study highlights ACSL3 as a prognostic biomarker for NSCLC, useful to select patients who would obtain a clinical benefit from statin administration.
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影响因子：
11.2
作者：
Jacobs, Eric J.;Newton, Christina C.;Gapstur, Susan M.
通讯作者：
Gapstur, Susan M.
影响因子：
64.8
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
22.7
作者：
Corsello, Steven M.;Nagari, Rohith T.;Golub, Todd R.
通讯作者：
Golub, Todd R.
DOI：
10.1073/pnas.1307237110
发表时间：
2013-05-28
影响因子：
11.1
作者：
Kamphorst, Jurre J.;Cross, Justin R.;Rabinowitz, Joshua D.
通讯作者：
Rabinowitz, Joshua D.
影响因子：
8.9
作者：
Grevengoed TJ;Klett EL;Coleman RA
通讯作者：
Coleman RA