Altered gene products involved in the malignant reprogramming of cancer stem/progenitor cells and multitargeted therapies

Murielle Mimeault, Surinder Kumar Batra

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Recent studies in the field of cancer stem cells have revealed that the alterations in key gene products involved in the epithelial-mesenchymal transition (EMT) program, altered metabolic pathways such as enhanced glycolysis, lipogenesis and/or autophagy and treatment resistance may occur in cancer stem/progenitor cells and their progenies during cancer progression. Particularly, the sustained activation of diverse developmental cascades such as hedgehog, epidermal growth factor receptor (EGFR), Wnt/β-catenin, Notch, transforming growth factor-β (TGF-β)/TGF-βR receptors and/or stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) can play critical functions for high self-renewal potential, survival, invasion and metastases of cancer stem/progenitor cells and their progenies. It has also been observed that cancer cells may be reprogrammed to re-express different pluripotency-associated stem cell-like markers such as Myc, Oct-3/4, Nanog and Sox-2 along the EMT process and under stressful and hypoxic conditions. Moreover, the enhanced expression and/or activities of some drug resistance-associated molecules such as Bcl-2, Akt/molecular target of rapamycin (mTOR), nuclear factor-kappaB (NF-κB), hypoxia-inducible factors (HIFs), macrophage inhibitory cytokine-1 (MIC-1) and ATP-binding cassette (ABC) multidrug transporters frequently occur in cancer cells during cancer progression and metastases. These molecular events may cooperate for the survival and acquisition of a more aggressive and migratory behavior by cancer stem/progenitor cells and their progenies during cancer transition to metastatic and recurrent disease states. Of therapeutic interest, these altered gene products may also be exploited as molecular biomarkers and therapeutic targets to develop novel multitargeted strategies for improving current cancer therapies and preventing disease relapse.

Original languageEnglish (US)
Pages (from-to)3-32
Number of pages30
JournalMolecular Aspects of Medicine
Volume39
DOIs
StatePublished - Oct 2014

    Fingerprint

Keywords

  • Biomarkers
  • Cancer stem/progenitor cells
  • Cancer-initiating cells
  • Epithelial-mesenchymal transition
  • Hypoxia
  • Metabolic pathways
  • Metastases
  • Metastasis-initiating cells
  • Multitargeted therapies
  • Personalized medicine
  • Therapeutic targets

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this