Notch1/TAZ axis promotes aerobic glycolysis and immune escape in lung cancer.
Notch1/TAZ axis promotes aerobic glycolysis and immune escape in lung cancer.
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Notch1/TAZ轴促进肺癌的有氧糖酵解和免疫逃逸。
DOI：
10.1038/s41419-021-04124-6
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发表时间：
2021-09-04
影响因子：
9
通讯作者：
Jiang K
中科院分区：
文献类型：
--
作者：
Xie M;Fu XG;Jiang K
致癌信号通路重新编程癌细胞代谢以促进有氧糖酵解，从而有利于肿瘤生长。癌细胞逃避免疫监视的能力和代谢调节剂在T细胞功能中的作用表明，癌基因诱导的代谢重编程可能与免疫逃逸有关。Notch 1信号在肺癌中失调，与糖酵解增加相关。在此，我们证明了在肺癌中Notch 1通过与组蛋白乙酰转移酶p300和pCAF的功能相互作用促进糖酵解基因的表达。Notch 1信号传导与TAZ形成正反馈回路。Notch 1转录活性在TAZ的存在下增加，并且激活是TEAD 1独立的。值得注意的是，有氧糖酵解对于Notch 1/TAZ轴调节体外和体内肺癌生长至关重要。通过Notch 1/TAZ轴增加细胞外乳酸水平抑制细胞毒性T细胞活性，导致肺癌细胞的侵袭性特征。Notch 1与TAZ相互作用促进肺癌有氧糖酵解和免疫逃逸我们的研究结果提供了针对Notch 1和TAZ的潜在治疗靶点，对肺癌的临床转化具有重要意义。
Oncogenic signaling pathway reprograms cancer cell metabolism to promote aerobic glycolysis in favor of tumor growth. The ability of cancer cells to evade immunosurveillance and the role of metabolic regulators in T-cell functions suggest that oncogene-induced metabolic reprogramming may be linked to immune escape. Notch1 signaling, dysregulated in lung cancer, is correlated with increased glycolysis. Herein, we demonstrate in lung cancer that Notch1 promotes glycolytic gene expression through functional interaction with histone acetyltransferases p300 and pCAF. Notch1 signaling forms a positive feedback loop with TAZ. Notch1 transcriptional activity was increased in the presence of TAZ and the activation was TEAD1 independent. Notably, aerobic glycolysis was critical for Notch1/TAZ axis modulation of lung cancer growth in vitro and in vivo. Increased level of extracellular lactate via Notch1/TAZ axis inhibited cytotoxic T-cell activity, leading to the invasive characteristic of lung cancer cells. Interaction between Notch1 and TAZ promoted aerobic glycolysis and immune escape in lung cancer. Our findings provide potential therapeutic targets against Notch1 and TAZ and would be important for clinical translation in lung cancer.
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影响因子：
11.2
作者：
Lim SO;Li CW;Xia W;Lee HH;Chang SS;Shen J;Hsu JL;Raftery D;Djukovic D;Gu H;Chang WC;Wang HL;Chen ML;Huo L;Chen CH;Wu Y;Sahin A;Hanash SM;Hortobagyi GN;Hung MC
通讯作者：
Hung MC
18F-FP-PEG2-β-Glu-RGD2：用于肿瘤 PET 成像的对称整合素 αvβ3 靶向放射性示踪剂
影响因子：
3.7
作者：
Hu K;Tang X;Tang G;Yao S;Yao B;Wang H;Nie D;Liang X;Tang C;He S
通讯作者：
He S
DOI：
10.1016/j.bbrc.2018.06.079
发表时间：
2018-09-05
影响因子：
3.1
作者：
Kuwabara, Shuhei;Yamaki, Misato;Itoh, Motoyuki
通讯作者：
Itoh, Motoyuki
影响因子：
37.8
作者：
Manderfield LJ;High FA;Engleka KA;Liu F;Li L;Rentschler S;Epstein JA
通讯作者：
Epstein JA
影响因子：
15.9
作者：
Kim, Wantae;Khan, Sanjoy Kumar;Yang, Yingzi
通讯作者：
Yang, Yingzi