Lactate Dehydrogenase B Controls Lysosome Activity and Autophagy in Cancer

被引：179

作者：

Brisson, Lucie ^{[1
]}

Banski, Piotr ^{[1
]}

Sboarina, Martina ^{[1
]}

Dethier, Coralie ^{[1
]}

Danhier, Pierre ^{[1
,2
]}

Fontenille, Marie-Josephine ^{[1
]}

Van Hee, Vincent F. ^{[1
]}

Vazeille, Thibaut ^{[1
]}

Tardy, Morgane ^{[1
]}

Falces, Jorge ^{[1
]}

Bouzin, Caroline ^{[3
]}

Porporato, Paolo E. ^{[1
]}

Frederick, Raphael ^{[2
]}

Michiels, Carine ^{[4
]}

Copetti, Tamara ^{[1
]}

Sonveaux, Pierre ^{[1
]}

机构：

[1] Catholic Univ Louvain, Pole Pharmacol, Inst Rech Expt & Clin, B-1200 Brussels, Belgium

[2] Catholic Univ Louvain, Louvain Drug Res Inst, B-1200 Brussels, Belgium

[3] Catholic Univ Louvain, IREC Imaging Platform, B-1200 Brussels, Belgium

[4] Univ Namur, URBC NARILIS, B-5000 Namur, Belgium

来源：

CANCER CELL | 2016年 / 30卷 / 03期

基金：

澳大利亚研究理事会;

关键词：

BREAST-CANCER; CELL-DEATH; TUMOR-CELLS; H SUBUNIT; EXPRESSION; PROTEIN; MITOCHONDRIAL; CHLOROQUINE; GROWTH; ANGIOGENESIS;

D O I：

10.1016/j.ccell.2016.08.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Metabolic adaptability is essential for tumor progression and includes cooperation between cancer cells with different metabolic phenotypes. Optimal glucose supply to glycolytic cancer cells occurs when oxidative cancer cells use lactate preferentially to glucose. However, using lactate instead of glucose mimics glucose deprivation, and glucose starvation induces autophagy. We report that lactate sustains autophagy in cancer. In cancer cells preferentially to normal cells, lactate dehydrogenase B (LDHB), catalyzing the conversion of lactate and NAD(+) to pyruvate, NADH and H+, controls lysosomal acidification, vesicle maturation, and intracellular proteolysis. LDHB activity is necessary for basal autophagy and cancer cell proliferation not only in oxidative cancer cells but also in glycolytic cancer cells.

引用

页码：418 / 431

页数：14

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