Stearoyl-CoA Desaturase 1 Potentiates Hypoxic plus Nutrient-Deprived Pancreatic Cancer Cell Ferroptosis Resistance.
Stearoyl-CoA Desaturase 1 Potentiates Hypoxic plus Nutrient-Deprived Pancreatic Cancer Cell Ferroptosis Resistance.
复制标题
硬脂酰辅酶A去饱和酶1增强低血糖和营养缺乏的胰腺癌细胞铁凋亡抗性。
DOI：
10.1155/2021/6629804
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发表时间：
2021
影响因子：
--
通讯作者：
Zhu H
中科院分区：
文献类型：
--
作者：
Gao J;Zhang Z;Liu Y;Zhang Z;Wang M;Gong A;Xia L;Liao X;Wang D;Zhu H
缺氧和营养缺乏(H/NS)微环境是胰腺癌的一个显著特征，在细胞死亡抵抗和肿瘤复发中起着关键作用。然而，它在铁性上睑下垂中的作用仍有待分类。在这里，我们发现H/NS通过改变细胞内的脂质成分来促进胰腺癌细胞对铁下垂的抵抗。在机制上，H/NS诱导硬脂酰辅酶A去饱和酶1(SCD1)表达上调，从而促进单不饱和脂肪酸(MUFAs)的合成，防止脂质过氧化。令人惊讶的是，SCD1与反铁下垂基因的表达有很强的相关性。此外，基于短发夹状RNA的SCD1基因敲除增强了体外H/NS条件下Erastin诱导的铁下垂。最后，我们的结果证实了erastin和一种特殊的scd1抑制剂A939572在预测胰腺癌皮下脂溢性死亡方面的协同作用。综上所述，我们的发现揭示了H/NS微环境抗铁下垂的新作用，并提出了克服胰腺癌细胞铁下垂抵抗的潜在治疗策略。
Hypoxia and nutrient starvation (H/NS) microenvironment, a notable characteristic of pancreatic carcinoma, plays a critical role in cell death resistance and tumor recurrence. However, its role in ferroptosis remains to be classified. Here, we found that H/NS contributed to the pancreatic cancer cell ferroptosis resistance depending on the altered intracellular lipid compositions. Mechanistically, H/NS induced the upregulation of stearoyl-CoA desaturase 1 (SCD1), which promoted monounsaturated fatty acids (MUFAs) synthesis and protected against lipid peroxidation. Surprisingly, SCD1 showed a strong correlation with antiferroptosis gene expression. Moreover, short-hairpin RNA-based knockdown of SCD1 enhanced erastin-induced ferroptosis in vitro under H/NS. Finally, our results demonstrate the synergistic effect of erastin and A939572, a special SCD1 inhibitor, in dictating pancreatic carcinoma subcutaneous ferroptotic death. Taken together, our findings reveal a new role of the H/NS microenvironment against ferroptosis and suggest a potential therapeutic strategy for overcoming ferroptosis resistance in pancreatic cancer cells.
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影响因子：
14.8
作者：
Doll S;Proneth B;Tyurina YY;Panzilius E;Kobayashi S;Ingold I;Irmler M;Beckers J;Aichler M;Walch A;Prokisch H;Trümbach D;Mao G;Qu F;Bayir H;Füllekrug J;Scheel CH;Wurst W;Schick JA;Kagan VE;Angeli JP;Conrad M
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8.8
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影响因子：
64.8
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影响因子：
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作者：
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