亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Lactate: A Metabolic Driver in the Tumour Landscape

免疫监视 糖酵解 癌细胞 生物 免疫系统 瓦博格效应 新陈代谢 癌症研究 肿瘤微环境 细胞 细胞信号 癌症 细胞生物学 生物化学 信号转导 免疫学 遗传学
作者
Luigi Ippolito,Andrea Morandi,Elisa Giannoni,Paola Chiarugi
出处
期刊:Trends in Biochemical Sciences [Elsevier BV]
卷期号:44 (2): 153-166 被引量:368
标识
DOI:10.1016/j.tibs.2018.10.011
摘要

In a tumour environment, lactate is no longer considered as a waste product from fermentative cell metabolism but instead as a powerful molecule that affects the behaviour of each cell surrounding and recruited to the tumour. Lactate establishes metabolic coupling between cancer cells and non-malignant cells, or among cancer cells themselves, thereby sustaining tumour growth. Lactate plays a key role in dampening immunosurveillance mediated by a plethora of immune cells recruited to the tumour site. Environmental lactate triggers signalling activation according to the cell subtype and its specific transporters/receptors. Targeting lactate metabolism and transport is a promising approach for cancer therapeutics. The presence of lactate in human tumours has been long neglected, confined to the role of a waste product derived from glycolysis and as a biomarker of malignancy. More recently, lactate has been rediscovered as signalling molecule that plays important roles in the regulation of the metabolic pathways, the immune response, and cell-to-cell communication within the tumour microenvironment. This review examines recent discoveries about the functional role of lactate in shaping the behaviour and the phenotype of tumour and tumour-associated cells, and describes potential clinical approaches to target lactate transport and metabolism in tumours. The presence of lactate in human tumours has been long neglected, confined to the role of a waste product derived from glycolysis and as a biomarker of malignancy. More recently, lactate has been rediscovered as signalling molecule that plays important roles in the regulation of the metabolic pathways, the immune response, and cell-to-cell communication within the tumour microenvironment. This review examines recent discoveries about the functional role of lactate in shaping the behaviour and the phenotype of tumour and tumour-associated cells, and describes potential clinical approaches to target lactate transport and metabolism in tumours. the dominant stromal cell type in solid tumours, with mesenchyme-like features and the phenotype of activated myofibroblasts. They participate in tumour progression by producing cytokines, chemokines, metabolites, enzymes, and extracellular matrix that sustain the growth of tumour cells. a family of proteins that transport glucose across the plasma membrane. a process in which glutamine is converted into glutamate, then entering the TCA cycle. a family of transcription factors that mediate metabolic and cellular responses to environmental changes such as hypoxia, oxidative stress, and nutrient metabolism. a transcription factor involved in the control of diverse cellular processes, including immune and inflammatory responses, cellular growth, and apoptosis. In the cytoplasm NF-κB binds to the inhibitor IκB in an inactive state; when IκB is phosphorylated and degraded, NF-κB translocates to the nucleus and drives gene expression. a branch from glycolysis – at the first step of glucose metabolism – that is essential for the synthesis of ribonucleotides and NADPH; the latter is required for the free radical scavenging system and is consumed during fatty acid synthesis. a family of iron- and 2-oxoglutarate-dependent dioxygenase enzymes that are involved in cellular adaptation to hypoxia and in the stability of collagen. a type of T cells that participate in the adaptive immune response and that differentiate into different subsets (TH1, TH2, TH17, and regulatory T cells; Tregs) as a function of specific stimuli. a cycle of aerobic reactions that provides energy by the oxidation of acetyl-CoA derived from sugars, lipids, or proteins. non-cancer or stromal cells and the extracellular matrix found in a tumour; the TME mainly comprises CAFs, blood vessels, and immune cells. a metabolic pathway that promotes high exploitation of glucose for rapid energy production and the flow of glycolytic intermediates into collateral pathways to synthesize nucleic acids, amino acids, and lipids, usually culminating in massive lactate production even under normoxic conditions.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
田様应助精明晓刚采纳,获得10
6秒前
32秒前
精明晓刚发布了新的文献求助10
38秒前
科研通AI2S应助科研通管家采纳,获得10
1分钟前
coolplex完成签到 ,获得积分10
2分钟前
wwe完成签到,获得积分10
2分钟前
貔貅完成签到 ,获得积分10
3分钟前
yindi1991完成签到 ,获得积分10
5分钟前
hgl完成签到,获得积分10
5分钟前
5分钟前
科研通AI2S应助科研通管家采纳,获得10
5分钟前
5分钟前
华仔应助精明晓刚采纳,获得10
6分钟前
6分钟前
6分钟前
精明晓刚发布了新的文献求助10
6分钟前
糖伯虎完成签到 ,获得积分10
7分钟前
在水一方应助科研通管家采纳,获得10
7分钟前
光合作用完成签到,获得积分10
8分钟前
8分钟前
精明晓刚发布了新的文献求助10
9分钟前
精明晓刚完成签到,获得积分10
9分钟前
9分钟前
搜集达人应助kangkang采纳,获得10
9分钟前
英姑应助科研通管家采纳,获得10
9分钟前
kangkang完成签到,获得积分20
10分钟前
10分钟前
刘紫媛发布了新的文献求助10
10分钟前
故意的冰淇淋完成签到 ,获得积分10
11分钟前
刘紫媛完成签到,获得积分20
11分钟前
Lucas应助Dave采纳,获得10
11分钟前
刘紫媛关注了科研通微信公众号
11分钟前
11分钟前
Akitten发布了新的文献求助10
11分钟前
草木完成签到 ,获得积分20
11分钟前
完美世界应助科研通管家采纳,获得10
11分钟前
领导范儿应助科研通管家采纳,获得10
11分钟前
Orange应助Boren采纳,获得10
12分钟前
12分钟前
Boren发布了新的文献求助10
12分钟前
高分求助中
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3990351
求助须知:如何正确求助?哪些是违规求助? 3532158
关于积分的说明 11256513
捐赠科研通 3271046
什么是DOI,文献DOI怎么找? 1805207
邀请新用户注册赠送积分活动 882302
科研通“疑难数据库(出版商)”最低求助积分说明 809234