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Novel Insights into PML-Dependent Oncosuppression

Lorenzo Galluzzi1

  • 1Department of Radiation Oncology, Weill Cornell Medical College, New York, NY 10065, USA; Equipe 11 Labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France; INSERM, U1138, 75006 Paris, France; Université Paris Descartes/Paris V, Sorbonne Paris Cité, 75006 Paris, France; Université Pierre et Marie Curie/Paris VI, 75006 Paris, France; Gustave Roussy Comprehensive Cancer Institute, 94805 Villejuif, France.

Trends in Cell Biology
|September 25, 2016
PubMed

Insights

Extranuclear promyelocytic leukemia suppresses autophagy, unlike its nuclear form, which may limit cancer progression. This suggests tumor suppressors can act in multiple cell compartments to fight cancer.

Area of Science:

  • Cell Biology
  • Oncology
  • Molecular Biology

Background:

  • Promyelocytic leukemia protein (PML) is known to function in the nucleus.
  • The role of extranuclear PML in cancer progression is less understood.

Purpose of the Study:

  • To investigate the function of extranuclear promyelocytic leukemia (PML) in cancer.
  • To determine the effect of extranuclear PML on autophagy.

Main Methods:

  • Immunofluorescence microscopy to visualize PML localization.
  • Autophagy assays to measure autophagic flux.
  • Cancer cell line experiments.

Main Results:

  • Extranuclear PML constitutively inhibits autophagy.
  • This inhibition of autophagy by extranuclear PML limits cancer progression.
  • Nuclear PML's role in autophagy regulation differs from its extranuclear counterpart.

Conclusions:

  • Extranuclear PML acts as a tumor suppressor by inhibiting autophagy.
  • Tumor suppressors may have specialized roles in different subcellular compartments.
  • Targeting extranuclear PML could be a strategy for cancer therapy.
Keywords:
MAMsautophagybeclin 1chloroquinep53regulated cell death

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