机构：[1]Institute of Pathology and Southwest Cancer Center, Southwest Hospital,Third Military Medical University (Army Medical University), and Key Laboratoryof Tumor Immunopathology, Ministry of Education of China, Chongqing,China[2]Department of Oncology, Sichuan Academy of Medical Sciences,Sichuan Provincial People’s Hospital, University of Electronic Science andTechnology of China, Chengdu, China四川省人民医院[3]Department of Oncology, ThirdAffiliated Hospital of Chongqing Medical University, Chongqing, China[4]Department of Oncology, Xinqiao Hospital, Third Military Medical University(Army Medical University), Chongqing, China[5]Department of Oncology,Chengdu Military General Hospital, Chengdu, China[6]Department of Oncology,The Affiliated Hospital of Southwest Medical University, Luzhou, China[7]Department of Dermatology, Chongqing Yubei District People’s Hospital,Chongqing, China[8]School of Life Science and Biopharmaceutics, ShenyangPharmaceutical University, Shenyang, China
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.
基金：
National Natural Science Foundation of China [81572892, 81302025, 81773040]; Sichuan Provincial Science Fund for Distinguished Young Scholars of China [2015JQO055]
第一作者机构：[1]Institute of Pathology and Southwest Cancer Center, Southwest Hospital,Third Military Medical University (Army Medical University), and Key Laboratoryof Tumor Immunopathology, Ministry of Education of China, Chongqing,China[2]Department of Oncology, Sichuan Academy of Medical Sciences,Sichuan Provincial People’s Hospital, University of Electronic Science andTechnology of China, Chengdu, China[3]Department of Oncology, ThirdAffiliated Hospital of Chongqing Medical University, Chongqing, China
共同第一作者：
通讯作者：
通讯机构：[1]Institute of Pathology and Southwest Cancer Center, Southwest Hospital,Third Military Medical University (Army Medical University), and Key Laboratoryof Tumor Immunopathology, Ministry of Education of China, Chongqing,China[2]Department of Oncology, Sichuan Academy of Medical Sciences,Sichuan Provincial People’s Hospital, University of Electronic Science andTechnology of China, Chengdu, China
推荐引用方式(GB/T 7714)：
Hongbo Zou,Qian Chen,Anmei Zhang,et al.MPC1 deficiency accelerates lung adenocarcinoma progression through the STAT3 pathway[J].CELL DEATH & DISEASE.2019,10:doi:10.1038/s41419-019-1324-8.
APA：
Hongbo Zou,Qian Chen,Anmei Zhang,SongtaoWang,Hong Wu...&Chuan Xu.(2019).MPC1 deficiency accelerates lung adenocarcinoma progression through the STAT3 pathway.CELL DEATH & DISEASE,10,
MLA：
Hongbo Zou,et al."MPC1 deficiency accelerates lung adenocarcinoma progression through the STAT3 pathway".CELL DEATH & DISEASE 10.(2019)
生物学