MPC1 deficiency accelerates lung adenocarcinoma progression through the STAT3 pathway.
MPC1 deficiency accelerates lung adenocarcinoma progression through the STAT3 pathway.
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MPC1 缺陷通过 STAT3 途径加速肺腺癌进展。
DOI：
10.1038/s41419-019-1324-8
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Xu Chuan
中科院分区：
文献类型：
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作者：
Zou Hongbo;Chen Qian;Zhang Anmei;Wang Songtao;Wu Hong;Yuan Ye;Wang Shuang;Yu Jing;Luo Mao;Wen Xianmei;Cui Wei;Fu Wenjuan;Yu Ruilian;Chen Lin;Zhang Ming;Lan Haitao;Zhang Xia;Xie Qichao;Jin Guoxiang;Xu Chuan
线粒体丙酮酸载体1（MPC 1）是控制丙酮酸在线粒体中转运的关键因子，已知在肿瘤发生和进展中经常失调。然而，MPC 1在肺腺癌（LAC）进展中的临床相关性和潜在分子机制仍有待阐明。因此，MPC 1在LAC组织中低表达，并与LAC患者的良好生存显著相关。在功能上，MPC 1显着抑制干细胞，入侵，并在体外迁移和蔓延生长的LAC细胞在体内。进一步研究发现，MPC 1可与线粒体信号转导子和转录激活子3（mito-STAT 3）相互作用，破坏STAT 3的分布，降低胞质信号转导子和转录激活子3（cyto-STAT 3）及其磷酸化水平，而IL-6激活cyto-STAT 3可逆转MPC 1过表达的LAC细胞的恶性进展。以上结果表明，MPC 1/STAT 3轴在LAC的发生发展中起重要作用，我们的研究可能为LAC的治疗提供新的思路。
Mitochondrial pyruvate carrier 1 (MPC1), a key factor that controls pyruvate transportation in the mitochondria, is known to be frequently dysregulated in tumor initiation and progression. However, the clinical relevance and potential molecular mechanisms of MPC1 in lung adenocarcinoma (LAC) progression remain to be illustrated. Herein, MPC1 was lowly expressed in LAC tissues and significantly associated with favorable survival of patients with LAC. Functionally, MPC1 markedly suppressed stemness, invasion, and migration in vitro and spreading growth of LAC cells in vivo. Further study revealed that MPC1 could interact with mitochondrial signal transducer and activator of transcription 3 (mito-STAT3), disrupting the distribution of STAT3 and reducing cytoplasmic signal transducer and activator of transcription 3 (cyto-STAT3) as well as its phosphorylation, while the activation of cyto-STAT3 by IL-6 reversed the attenuated malignant progression in MPC1-overexpression LAC cells. Collectively, we reveal that MPC1/STAT3 axis plays an important role in the progression of LAC, and our work may promote the development of new therapeutic strategies for LAC.