机构：[1]Institute of Drug Clinical Trial, State Key Laboratory of Biotherapy and CancerCenter, West China Hospital, Sichuan University, Chengdu 610041, China四川大学华西医院[2]Department of Oncology and Southwest Cancer Center, Southwest Hospital,Third Military Medical University (Army Medical University), Chongqing, China[3]Department of biochemistry, Tokyo medical University, Tokyo, Japan[4]Vascular Program, Institute for Cell Engineering, Johns Hopkins UniversitySchool of Medicine, Baltimore, MD 21205, USA[5]McKusick-Nathans Institute ofGenetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD21205, USA[6]Departments of Pediatrics, Medicine, Oncology, RadiationOncology, and Biological Chemistry, Johns Hopkins University School ofMedicine, Baltimore, MD 21205, USA
Cancer cells re-program their metabolic machinery to meet the requirements of malignant transformation and progression. Glutaminase 1 (GLS1) was traditionally known as a mitochondrial enzyme that hydrolyzes glutamine into glutamate and fuels rapid proliferation of cancer cells. However, emerging evidence has now revealed that GLS1 might be a novel oncogene involved in tumorigenesis and progression of human cancers. In this study, we sought to determine whether GLS1 implicated in invasion and metastasis of colorectal carcinoma, and its underlying molecular mechanism. By analyzing a large set of clinical data from online datasets, we found that GLS1 is overexpressed in cancers compared with adjacent normal tissues, and associated with increased patient mortality. Immunohistochemical analysis of GLS1 staining showed that high GLS1 expression is significantly correlated with lymph node metastasis and advanced clinical stage in colorectal cancer patients. To investigate the underlying mechanism, we analyzed the Cancer Genome Atlas database and found that GLS1 mRNA expression is associated with a hypoxia signature, which is correlated with an increased risk of metastasis and mortality. Furthermore, reduced oxygen availability increases GLS1 mRNA and protein expression, due to transcriptional activation by hypoxia-inducible factor 1. GLS1 expression in colorectal cancer cells is required for hypoxia-induced migration and invasion in vitro and for tumor growth and metastatic colonization in vivo.
基金：
the National Natural Science Foundation of China
(NSFC No. 81402526 and NSFC No. 81301841), the Natural Science Foundation
of Chongqing (No. cstc2018jcyjAX0512), the China Postdoctoral Science
Foundation (CPSF No. 2016M590892), and the Technology Innovation Project
of Military Medicine (SWH2017JCZD-09).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|2 区生物学
小类|2 区细胞生物学
最新[2023]版：
大类|1 区生物学
小类|2 区细胞生物学
第一作者：
第一作者机构：[1]Institute of Drug Clinical Trial, State Key Laboratory of Biotherapy and CancerCenter, West China Hospital, Sichuan University, Chengdu 610041, China
通讯作者：
推荐引用方式(GB/T 7714)：
Lisha Xiang,Jun Mou,Bin Shao,et al.Glutaminase 1 expression in colorectal cancer cells is induced by hypoxia and required for tumor growth, invasion, and metastatic colonization.[J].Cell death & disease.2019,10(2):40.doi:10.1038/s41419-018-1291-5.
APA：
Lisha Xiang,Jun Mou,Bin Shao,Yuquan Wei,Houjie Liang...&Ganfeng Xie.(2019).Glutaminase 1 expression in colorectal cancer cells is induced by hypoxia and required for tumor growth, invasion, and metastatic colonization..Cell death & disease,10,(2)
MLA：
Lisha Xiang,et al."Glutaminase 1 expression in colorectal cancer cells is induced by hypoxia and required for tumor growth, invasion, and metastatic colonization.".Cell death & disease 10..2(2019):40
生物学