Warburg effect in Gynecologic cancers

Yusuke Kobayashi, Kouji Banno, Haruko Kunitomi, Takayuki Takahashi, Takashi Takeda, Kanako Nakamura, Kosuke Tsuji, Eiichirou Tominaga, Daisuke Aoki

Research output: Contribution to journalArticle

Abstract

Mammalian cells produce energy by oxidative phosphorylation under aerobic conditions. However, in the 1920s, Otto Warburg reported the so-called “Warburg effect” in which cancer cells produce ATP that is biased toward glycolysis rather than mitochondrial oxidative phosphorylation not only in anaerobic environment but also in aerobic environment. Glucose is converted into lactate without going into mitochondria after being metabolized in glycolysis. Compared with oxidative phosphorylation, the glycolysis has a faster ATP production rate but it is very inefficient, resulting in cancer cells consuming a large amount of glucose. Increased glucose metabolism has become a biomarker for cancer cells and has led to the development of positron emission tomography with fluorodeoxyglucose. Till date, the Warburg effect has been an inefficient system for cancer cells with regard to efficient energy production, but since the consumption of oxygen can be suppressed as the tumor grows in mass, it is thought that the Warburg effect is advantageous in this situation wherein the tumor can increase despite the lack of vessels. In addition, an increased lactate by the glycolysis causes acidosis in the microenvironment of tissues, which is thought to damage the surrounding normal tissues and favor the invasion and metastasis of cancer. Thus, Warburg effect is one of the key mechanisms for cancer development and will be the next promising target. In this review, we introduce key players that can be targeted in the Warburg effect and outline the prospects of treatment, targeting the Warburg effect in gynecological cancer.

Original languageEnglish
JournalJournal of Obstetrics and Gynaecology Research
DOIs
Publication statusAccepted/In press - 2018 Jan 1

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Keywords

  • drug repositioning
  • glycolysis
  • oxidative phosphorylation
  • reverse Warburg effect
  • Warburg effect

ASJC Scopus subject areas

  • Obstetrics and Gynaecology

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