Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells.
Metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation in platinum-resistant cancer cells.
复制标题
DOI：
10.1038/s41467-022-32101-w
复制
发表时间：
2022-08-05
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
糖酵解增加被认为是癌症的标志。然而，在治疗抗性发展过程中的癌细胞代谢重编程研究不足。在这里，通过高通量受激拉曼散射成像和单细胞分析，我们发现顺铂耐药细胞表现出增加的脂肪酸（FA）摄取，伴随着减少的葡萄糖摄取和脂肪生成，表明从葡萄糖到FA依赖的合成代谢和能量代谢的重编程。结合葡萄糖衍生的抗肿瘤和FA摄取的代谢指数与卵巢癌（OC）细胞系和原代细胞中的顺铂抗性水平线性相关。增加的FA摄取通过增强β-氧化促进顺铂诱导的氧化应激下的癌细胞存活。因此，通过与顺铂或卡铂组合的小分子抑制剂阻断β-氧化协同抑制体外OC增殖和体内患者来源的异种移植物的生长。总的来说，这些发现支持在单细胞水平上快速检测顺铂耐药性的方法和治疗顺铂耐药肿瘤的策略。代谢重编程与癌症的发生、进展和对治疗的抵抗有关。在这里，作者表明，从糖酵解到脂肪酸摄取和β-氧化的代谢重编程与癌细胞铂类化疗耐药性有关。
Increased glycolysis is considered as a hallmark of cancer. Yet, cancer cell metabolic reprograming during therapeutic resistance development is under-studied. Here, through high-throughput stimulated Raman scattering imaging and single cell analysis, we find that cisplatin-resistant cells exhibit increased fatty acids (FA) uptake, accompanied by decreased glucose uptake and lipogenesis, indicating reprogramming from glucose to FA dependent anabolic and energy metabolism. A metabolic index incorporating glucose derived anabolism and FA uptake correlates linearly to the level of cisplatin resistance in ovarian cancer (OC) cell lines and primary cells. The increased FA uptake facilitates cancer cell survival under cisplatin-induced oxidative stress by enhancing beta-oxidation. Consequently, blocking beta-oxidation by a small molecule inhibitor combined with cisplatin or carboplatin synergistically suppresses OC proliferation in vitro and growth of patient-derived xenografts in vivo. Collectively, these findings support a rapid detection method of cisplatin-resistance at single cell level and a strategy for treating cisplatin-resistant tumors. Metabolic reprogramming is associated with cancer initiation, progression and resistance to therapy. Here, the authors show that metabolic reprogramming from glycolysis to fatty acid uptake and beta-oxidation is associated with cancer-cell platinum-based chemotherapy resistance.
登录
查看更多内容
影响因子：
28.5
作者：
Dong R;Qiang W;Guo H;Xu X;Kim JJ;Mazar A;Kong B;Wei JJ
通讯作者：
Wei JJ
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
48
作者：
Hu, Fanghao;Shi, Lixue;Min, Wei
通讯作者：
Min, Wei
溶血磷脂酰胆碱酰基转移酶2介导的脂质液滴生产支持结直肠癌的化学耐药性。
影响因子：
16.6
作者：
Cotte AK;Aires V;Fredon M;Limagne E;Derangère V;Thibaudin M;Humblin E;Scagliarini A;de Barros JP;Hillon P;Ghiringhelli F;Delmas D
通讯作者：
Delmas D
影响因子：
8
作者：
通讯作者：
--