Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
Department of Oncology, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Cell Death Dis. 2019 Feb 15;10(3):148. doi: 10.1038/s41419-019-1324-8.
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.
线粒体丙酮酸载体 1（MPC1）是控制线粒体中丙酮酸运输的关键因素，已知其在肿瘤起始和进展中经常失调。然而，MPC1 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。在此，MPC1 在 LAC 组织中低表达，并与 LAC 患者的良好生存显著相关。功能上，MPC1 显著抑制体外干细胞特性、侵袭和迁移以及体内 LAC 细胞的扩散生长。进一步的研究表明，MPC1 可以与线粒体信号转导和转录激活因子 3（mito-STAT3）相互作用，破坏 STAT3 的分布，减少细胞质信号转导和转录激活因子 3（cyto-STAT3）及其磷酸化，而 IL-6 激活的 cyto-STAT3 则逆转了 MPC1 过表达 LAC 细胞中减弱的恶性进展。综上所述，我们揭示了 MPC1/STAT3 轴在 LAC 进展中发挥重要作用，我们的工作可能为 LAC 的治疗策略的发展提供新的思路。
