Role of autophagy in the maintenance and function of cancer stem cells

Ilio Vitale, Gwenola Manic, Vito Dandrea, Ruggero De Maria

Research output: Contribution to journalArticle

Abstract

Recent advances in experimental technologies and cancer models have made possible to demonstrate that the tumor is a dynamic system comprising heterogeneous populations of cancer cells organized in a hierarchical fashion with cancer stem cells (CSCs) at the apex. CSCs are immature cells characterized by self-renewal property and long-term repopulation potential. CSCs have been causally linked to cancer initiation, propagation, spreading, recurrence and relapse as well as to resistance to anticancer therapy. A growing body of evidence suggests that the function and physiology of CSCs may be influenced by genetic/epigenetic factors and tumor environment. In this context, macroautophagy is a lysosomal degradative process (herein referred to as autophagy) critical for the adaptive response to stress and the preservation of cellular and tissue homeostasis in all eukaryotes that may have a crucial role of in the origin, maintenance and invasiveness of CSCs. The activation of the autophagic machinery is also considered as an adaptive response of CSCs to perturbation of tumor microenvironment, caused for instance by anticancer therapy. Nevertheless, compelling preclinical and clinical evidence on the cytoprotective role of autophagy for CSCs is still missing. Here, we summarize the results on the contribution of autophagy in CSCs and how it impacts tumorigenesis and tumor progression. We also discuss the therapeutical potential of the modulation of autophagy as a means to eradicate CSCs.

Original languageEnglish
Pages (from-to)95-108
Number of pages14
JournalInternational Journal of Developmental Biology
Volume59
Issue number1-3
DOIs
Publication statusPublished - Sep 3 2015

Keywords

  • Autophagosomes
  • Beclin 1
  • CD133
  • Chloroquine
  • Lysosomes
  • Tumor initiating cells

ASJC Scopus subject areas

  • Developmental Biology
  • Embryology

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