Hypoxia optimises tumour growth by controlling nutrient import and acidic metabolite export

被引：53
作者：
Parks, Scott K. [1 ]
Cormerais, Yann [1 ]
Marchiq, Ibtissam [2 ]
Pouyssegur, Jacques [1 ,2 ]
机构：
[1] CSM, Monaco, Monaco
[2] Univ Nice Sophia Antipolis, INSERM, CNRS, Inst Res Canc & Aging IRCAN, F-06189 Nice, France
来源：
MOLECULAR ASPECTS OF MEDICINE | 2016年 / 47-48卷
基金：
欧盟第七框架计划;
关键词：
hypoxia; tumour metabolism; amino-acid transport (LAT1); tumour pH regulation; carbonic anhydrases (CAs); monocarboxylate transporters (MCTs); HCO(3)(-)transport; CARBONIC-ANHYDRASE-IX; BREAST-CANCER CELLS; MONOCARBOXYLATE TRANSPORTER MCT4; TRANSFER-RNA SYNTHETASE; SURFACE-PH TRANSIENTS; ENHANCES CO2 FLUXES; INTRACELLULAR PH; IN-VIVO; THERAPEUTIC TARGET; AEROBIC GLYCOLYSIS;
D O I：
10.1016/j.mam.2015.12.001
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
In their quest for survival and successful growth, cancer cells optimise their cellular processes to enable them to outcompete normal cells in their microenvironment. In essence cancer cells: (i) enhance uptake of nutrients/metabolites, (ii) utilise nutrients more efficiently via metabolic alterations and (iii) deal with the metabolic waste products in a way that furthers their progression while hampering the survival of normal tissue. Hypoxia Inducible Factors (HIFs) act as essential drivers of these adaptations via the promotion of numerous membrane proteins including glucose transporters (GLUTs), monocarboxylate transporters (MCTs), amino-acid transporters (LAT1, xCT), and acid-base regulating carbonic anhydrases (CAs). In addition to a competitive growth advantage for tumour cells, these HIF-regulated proteins are implicated in metastasis, cancer 'stemness' and the immune response. Current research indicates that combined targeting of these HIF-regulated membrane proteins in tumour cells will provide promising therapeutic strategies in the future. (C) 2015 Elsevier Ltd. All rights reserved.
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收藏
页码：3 / 14
页数：12
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