Nodal promotes colorectal cancer survival and metastasis through regulating SCD1-mediated ferroptosis resistance.
Nodal promotes colorectal cancer survival and metastasis through regulating SCD1-mediated ferroptosis resistance.
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Nodal通过调节SCD 1介导的铁凋亡抵抗促进结直肠癌生存和转移
DOI：
10.1038/s41419-023-05756-6
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发表时间：
2023-03-31
影响因子：
9
通讯作者：
Yin, Lu
中科院分区：
文献类型：
--
作者：
Wu, Tianqi;Wan, Jian;Qu, Xiao;Xia, Kai;Wang, Fangtao;Zhang, Zichao;Yang, Muqing;Wu, Xiaocai;Gao, Renyuan;Yuan, Xiaoqi;Fang, Lin;Chen, Chunqiu;Yin, Lu
胚胎形态原Nodal的重新表达在几种类型的恶性肿瘤中都可以看到。到目前为止，关于Nodal在结直肠癌(CRC)中的作用的研究仍然有限。铁性下垂是结直肠癌进展所必需的，它是由细胞氧化还原失衡引起的，以脂质过氧化为特征。在此，我们观察到Nodal在体内和体外都增强了结直肠癌细胞的增殖率、移动性、侵袭性和上皮-间充质转化(EMT)。值得注意的是，Nodal的过度表达诱导了单不饱和脂肪酸的合成，并增加了脂质不饱和水平。结节敲除导致结直肠癌细胞脂质过氧化增加。硬脂酰辅酶A去饱和酶1(SCD1)的抑制至少部分地消除了Nodal过表达细胞对RSL3诱导的铁性下垂的抵抗力。从机制上讲，Smad2/3途径的激活反应于Nodal的过表达，在转录水平上上调了SCD1的表达。在结直肠癌组织中观察到显著的Nodal和SCD1表达上调，并与结直肠癌转移和不良的临床预后相关。此外，靶向Nodal的牛血清白蛋白纳米粒/硅结节纳米复合体对结直肠癌的进展和转移具有抗肿瘤作用。这项研究阐明了Nodal在结直肠癌发生发展中的作用，并揭示了针对Nodal的潜在基因治疗策略，以改善结直肠癌的治疗。
Re-expression of an embryonic morphogen, Nodal, has been seen in several types of malignant tumours. By far, studies about Nodal’s role in colorectal cancer (CRC) remain limited. Ferroptosis is essential for CRC progression, which is caused by cellular redox imbalance and characterized by lipid peroxidation. Herein, we observed that Nodal enhanced CRC cell’s proliferative rate, motility, invasiveness, and epithelial–mesenchymal transition (EMT) in vivo and in vitro. Notably, Nodal overexpression induced monounsaturated fatty acids synthesis and increased the lipid unsaturation level. Nodal knockdown resulted in increased CRC cell lipid peroxidation. Stearoyl-coenzyme A desaturase 1 (SCD1) inhibition at least partially abolished the resistance of Nodal-overexpressing cells to RSL3-induced ferroptosis. Mechanistically, SCD1 was transcriptionally up-regulated by Smad2/3 pathway activation in response to Nodal overexpression. Significant Nodal and SCD1 up-regulation were observed in CRC tissues and were associated with CRC metastasis and poor clinical outcomes. Furthermore, bovine serum albumin nanoparticles/si-Nodal nanocomplexes targeting Nodal had anti-tumour effects on CRC progression and metastasis. This research elucidated the role of Nodal in CRC development and revealed a potential gene-based therapeutic strategy targeting Nodal for improving CRC treatment.
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影响因子：
14.8
作者：
Kagan VE;Mao G;Qu F;Angeli JP;Doll S;Croix CS;Dar HH;Liu B;Tyurin VA;Ritov VB;Kapralov AA;Amoscato AA;Jiang J;Anthonymuthu T;Mohammadyani D;Yang Q;Proneth B;Klein-Seetharaman J;Watkins S;Bahar I;Greenberger J;Mallampalli RK;Stockwell BR;Tyurina YY;Conrad M;Bayır H
通讯作者：
Bayır H
影响因子：
5.8
作者：
Alwhaibi, Abdulrahman;Verma, Arti;Somanath, Payaningal R.
通讯作者：
Somanath, Payaningal R.
Nodal 通过抑制氧化应激和炎症减轻脑缺血再灌注损伤
DOI：
10.26355/eurrev_201907_18337
发表时间：
2019-07-01
影响因子：
3.3
作者：
Cui, Y.;Wang, J-Q;Xu, Z-X
通讯作者：
Xu, Z-X
影响因子：
15.9
作者：
Lai, Jing-Huei;Jan, Hsun-Jin;Ma, Hsin-I
通讯作者：
Ma, Hsin-I
DOI：
10.1016/j.neo.2021.02.004
发表时间：
2021-04
期刊：
Neoplasia (New York, N.Y.)
影响因子：
--
作者：
Dieters-Castator D;Dantonio PM;Piaseczny M;Zhang G;Liu J;Kuljanin M;Sherman S;Jewer M;Quesnel K;Kang EY;Köbel M;Siegers GM;Leask A;Hess D;Lajoie G;Postovit LM
通讯作者：
Postovit LM