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The dual role of autophagy in cancer

Eeva-Liisa Eskelinen1

  • 1University of Helsinki, Department of Biosciences, Helsinki, Finland. eeva-liisa.eskelinen@helsinki.fi

Current Opinion in Pharmacology
|April 19, 2011
PubMed

Insights

Autophagy, a cellular recycling process, can suppress tumors by clearing damaged components. However, cancer cells hijack autophagy for survival and treatment resistance, highlighting it as a therapeutic target.

Area of Science:

  • Cellular Biology
  • Oncology
  • Molecular Mechanisms

Background:

  • Autophagy is a cellular degradation process involving lysosomes, crucial for clearing cytoplasmic material, damaged organelles, and aggregate-prone proteins.
  • Autophagy acts as a tumor suppressor by clearing p62/SQSTM1, preventing oxidative stress and genomic instability.
  • Conversely, cancer cells exploit autophagy for survival under nutrient deprivation and hypoxia, and to resist cancer treatments.

Purpose of the Study:

  • To explore the dual role of autophagy in cancer, acting as both a tumor suppressor and a facilitator of tumor cell survival and treatment resistance.
  • To investigate the specific mechanisms by which cancer cells utilize autophagy.
  • To examine the potential of targeting autophagy as a therapeutic strategy in oncology.

Main Methods:

  • Review of recent evidence and studies on autophagy's role in tumorigenesis and cancer progression.
  • Analysis of autophagy's involvement in cellular responses to stress conditions like nutrient limitation and hypoxia.
  • Examination of autophagy's role in mediating resistance to cancer therapies, including radiation therapy.

Main Results:

  • Autophagy's tumor-suppressive functions are linked to the clearance of p62/SQSTM1 and maintenance of genomic stability.
  • Cancer cells upregulate autophagy to survive harsh tumor microenvironments and treatment-induced stress.
  • Inhibition of autophagy can enhance the efficacy of cancer treatments by overcoming treatment resistance.

Conclusions:

  • Autophagy presents a complex role in cancer, with context-dependent tumor-suppressive and pro-survival functions.
  • Targeting autophagy is a promising strategy to enhance cancer treatment outcomes, particularly in overcoming resistance.
  • Specific molecular players, such as FK506-binding protein 51, are implicated in autophagy-mediated resistance, offering potential therapeutic targets.

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