HAO1-mediated oxalate metabolism promotes lung pre-metastatic niche formation by inducing neutrophil extracellular traps.
HAO1-mediated oxalate metabolism promotes lung pre-metastatic niche formation by inducing neutrophil extracellular traps.
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HAO1介导的草酸代谢通过诱导中性粒细胞胞外陷阱促进肺转移前生态位形成
DOI：
10.1038/s41388-022-02248-3
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发表时间：
2022-07
期刊：
影响因子：
8
通讯作者：
Liang, Li
中科院分区：
文献类型：
--
作者：
Zeng, Zhicheng;Xu, Shaowan;Wang, Feifei;Peng, Xin;Zhang, Wanning;Zhan, Yizhi;Ding, Yanqing;Liu, Ziguang;Liang, Li
代谢重编程已被证明参与癌症诱导的转移前小生境（PMN）形成，但其潜在机制尚未得到充分探讨。在这里，我们发现，羟酸氧化酶1（HAO 1），草酸合成的限速酶，在转移前阶段携带转移性乳腺癌细胞的小鼠肺泡上皮细胞中上调，导致肺组织中草酸盐的积累。肺草酸盐蓄积通过激活NADPH氧化酶诱导中性粒细胞细胞外陷阱（NET）形成，促进转移前小生境的形成。此外，肺草酸盐积聚通过激活MAPK信号通路促进转移性癌细胞的增殖。HAO 1的药理学抑制作用可有效抑制原发癌诱导的肺草酸盐蓄积，从而抑制乳腺癌的肺转移。乳腺癌细胞通过激活TLR 3-IRF 3信号诱导肺泡上皮细胞HAO 1表达和草酸盐积累。总的来说，这些发现强调了HAO 1介导的草酸盐代谢在癌症诱导的肺PMN形成和转移中的作用。HAO 1可能成为一个有吸引力的预防肿瘤肺转移的治疗靶点。
Metabolic reprogramming has been shown to be involved in cancer-induced pre-metastatic niche (PMN) formation, but the underlying mechanisms have been insufficiently explored. Here, we showed that hydroxyacid oxidase 1 (HAO1), a rate-limiting enzyme of oxalate synthesis, was upregulated in the alveolar epithelial cells of mice bearing metastatic breast cancer cells at the pre-metastatic stage, leading to oxalate accumulation in lung tissue. Lung oxalate accumulation induced neutrophil extracellular trap (NET) formation by activating NADPH oxidase, which facilitated the formation of pre-metastatic niche. In addition, lung oxalate accumulation promoted the proliferation of metastatic cancer cells by activating the MAPK signaling pathway. Pharmacologic inhibition of HAO1 could effectively suppress the lung oxalate accumulation induced by primary cancer, consequently dampening lung metastasis of breast cancer. Breast cancer cells induced HAO1 expression and oxalate accumulation in alveolar epithelial cells by activating TLR3-IRF3 signaling. Collectively, these findings underscore the role of HAO1-mediated oxalate metabolism in cancer-induced lung PMN formation and metastasis. HAO1 could be an appealing therapeutic target for preventing lung metastasis of cancer.
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影响因子：
3.8
作者：
Castellaro AM;Tonda A;Cejas HH;Ferreyra H;Caputto BL;Pucci OA;Gil GA
通讯作者：
Gil GA
DOI：
10.1016/j.neo.2015.08.005
发表时间：
2015-08
期刊：
Neoplasia (New York, N.Y.)
影响因子：
--
作者：
Simões RV;Serganova IS;Kruchevsky N;Leftin A;Shestov AA;Thaler HT;Sukenick G;Locasale JW;Blasberg RG;Koutcher JA;Ackerstaff E
通讯作者：
Ackerstaff E
影响因子：
82.9
作者：
Sistigu, Antonella;Yamazaki, Takahiro;Zitvogel, Laurence
通讯作者：
Zitvogel, Laurence
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
32.4
作者：
Teijeira, Alvaro;Garasa, Saray;Melero, Ignacio
通讯作者：
Melero, Ignacio