Redox regulation in stem-like cancer cells by CD44 variant isoforms

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Increasing evidence indicates that several types of solid tumor are hierarchically organized and sustained by a distinct population of cancer stem cells (CSCs). CSCs possess enhanced mechanisms of protection from stress induced by reactive oxygen species (ROS) that render them resistant to chemo-and radiotherapy. Expression of CD44, especially variant isoforms (CD44v) of this major CSC marker, contributes to ROS defense through upregulation of the synthesis of reduced glutathione (GSH), the primary intracellular antioxidant. CD44v interacts with and stabilizes xCT, a subunit of the cystine-glutamate transporter xc(-), and thereby promotes cystine uptake for GSH synthesis. Given that cancer cells are often exposed to high levels of ROS during tumor progression, the ability to avoid the consequences of such exposure is required for cancer cell survival and propagation in vivo. CSCs, in which defense against ROS is enhanced by CD44v are thus thought to drive tumor growth, chemoresistance and metastasis. Therapy targeted to the CD44v-xCT system may therefore impair the ROS defense ability of CSCs and thereby sensitize them to currently available treatments.

Original languageEnglish
Pages (from-to)5191-5198
Number of pages8
JournalOncogene
Volume32
Issue number44
DOIs
Publication statusPublished - 2013 Oct 31

Fingerprint

Neoplastic Stem Cells
Oxidation-Reduction
Reactive Oxygen Species
Protein Isoforms
Cystine
Neoplasms
Amino Acid Transport System X-AG
Glutathione
Cell Survival
Up-Regulation
Radiotherapy
Antioxidants
Neoplasm Metastasis
Therapeutics
Growth
Population

Keywords

  • cancer stem cell
  • CD44
  • cystine-glutamate transporter
  • reactive oxygen species

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Redox regulation in stem-like cancer cells by CD44 variant isoforms. / Nagano, Osamu; Okazaki, S.; Saya, Hideyuki.

In: Oncogene, Vol. 32, No. 44, 31.10.2013, p. 5191-5198.

Research output: Contribution to journalArticle

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