Journal
CANCER RESEARCH
Volume 72, Issue 6, Pages 1438-1448Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-11-3024
Keywords
-
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan
- MEXT, Japan
- Grants-in-Aid for Scientific Research [23790376, 22700865, 22710222, 22130007, 11J55543] Funding Source: KAKEN
Ask authors/readers for more resources
An increased glycolytic flux accompanied by activation of the pentose phosphate pathway (PPP) is implicated in chemoresistance of cancer cells. In this study, we found that CD44, a cell surface marker for cancer stem cells, interacts with pyruvate kinase M2 (PKM2) and thereby enhances the glycolytic phenotype of cancer cells that are either deficient in p53 or exposed to hypoxia. CD44 ablation by RNA interference increased metabolic flux to mitochondrial respiration and concomitantly inhibited entry into glycolysis and the PPP. Such metabolic changes induced by CD44 ablation resulted in marked depletion of cellular reduced glutathione (GSH) and increased the intracellular level of reactive oxygen species in glycolytic cancer cells. Furthermore, CD44 ablation enhanced the effect of chemotherapeutic drugs in p53-deficient or hypoxic cancer cells. Taken together, our findings suggest. that metabolic modulation by Call is a potential therapeutic target for glycolytic cancer cells that manifest drug resistance. Cancer Res; 72(6);1438-48. (C) 2012 AACR
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available