Modulation of glucose metabolism by CD44 contributes to antioxidant status and drug resistance in cancer cells

Mayumi Tamada; Osamu Nagano; Seiji Tateyama; Mitsuyo Ohmura; Toshifumi Yae; Takatsugu Ishimoto; Eiji Sugihara; Nobuyuki Onishi; Takehiro Yamamoto; Hiroshi Yanagawa; Makoto Suematsu; Hideyuki Saya

doi:10.1158/0008-5472.CAN-11-3024

Modulation of glucose metabolism by CD44 contributes to antioxidant status and drug resistance in cancer cells

Mayumi Tamada, Osamu Nagano, Seiji Tateyama, Mitsuyo Ohmura, Toshifumi Yae, Takatsugu Ishimoto, Eiji Sugihara, Nobuyuki Onishi, Takehiro Yamamoto, Hiroshi Yanagawa, Makoto Suematsu, Hideyuki Saya

Cancer Center

Research output: Contribution to journal › Article

134 Citations (Scopus)

Abstract

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 CD44 is a potential therapeutic target for glycolytic cancer cells that manifest drug resistance.

Original language	English
Pages (from-to)	1438-1448
Number of pages	11
Journal	Cancer Research
Volume	72
Issue number	6
DOIs	https://doi.org/10.1158/0008-5472.CAN-11-3024
Publication status	Published - 15-03-2012

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

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Tamada, M., Nagano, O., Tateyama, S., Ohmura, M., Yae, T., Ishimoto, T., Sugihara, E., Onishi, N., Yamamoto, T., Yanagawa, H., Suematsu, M., & Saya, H. (2012). Modulation of glucose metabolism by CD44 contributes to antioxidant status and drug resistance in cancer cells. Cancer Research, 72(6), 1438-1448. https://doi.org/10.1158/0008-5472.CAN-11-3024

Tamada, Mayumi ; Nagano, Osamu ; Tateyama, Seiji ; Ohmura, Mitsuyo ; Yae, Toshifumi ; Ishimoto, Takatsugu ; Sugihara, Eiji ; Onishi, Nobuyuki ; Yamamoto, Takehiro ; Yanagawa, Hiroshi ; Suematsu, Makoto ; Saya, Hideyuki. / Modulation of glucose metabolism by CD44 contributes to antioxidant status and drug resistance in cancer cells. In: Cancer Research. 2012 ; Vol. 72, No. 6. pp. 1438-1448.

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Modulation of glucose metabolism by CD44 contributes to antioxidant status and drug resistance in cancer cells. / Tamada, Mayumi; Nagano, Osamu; Tateyama, Seiji; Ohmura, Mitsuyo; Yae, Toshifumi; Ishimoto, Takatsugu; Sugihara, Eiji; Onishi, Nobuyuki; Yamamoto, Takehiro; Yanagawa, Hiroshi; Suematsu, Makoto; Saya, Hideyuki.

In: Cancer Research, Vol. 72, No. 6, 15.03.2012, p. 1438-1448.

Research output: Contribution to journal › Article

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