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A novel role for a glycolytic pathway kinase in regulating autophagy has implications in cancer therapy

Aileen R Ariosa1, Daniel J Klionsky1

  • 1a Life Sciences Institute, University of Michigan , Ann Arbor , MI , USA.

Autophagy
|May 25, 2017
PubMed

Insights

Autophagy plays a dual role in cancer, potentially suppressing tumors or promoting their growth. A new study reveals how the glycolytic enzyme PGK1 regulates autophagy in cancer cells under stress.

Area of Science:

  • Cell Biology
  • Oncology
  • Biochemistry

Background:

  • Macroautophagy/autophagy exhibits context-dependent roles in cancer, acting as both a tumor suppressor and a promoter of cancer progression.
  • Understanding the regulatory mechanisms of autophagy is critical for developing targeted anticancer therapies.

Purpose of the Study:

  • To identify key regulatory pathways governing autophagy induction in tumorigenic cells under conditions of hypoxia and glutamine deprivation.
  • To elucidate the role of posttranslational modifications in modulating autophagic flux in cancer.

Main Methods:

  • Investigated the interplay between the glycolytic pathway and autophagy regulation.
  • Utilized biochemical assays to analyze protein phosphorylation and its impact on autophagosome formation.
  • Examined the role of phosphatidylinositol 3-kinase (PtdIns3K) complex activity in response to cellular stress.

Main Results:

  • Discovered that the glycolytic enzyme PGK1 phosphorylates BECN1, a key scaffolding protein in autophagy.
  • Demonstrated that this phosphorylation enhances the activity of the class III PtdIns3K complex, leading to increased PtdIns3P production.
  • Showed that this cascade is crucial for hypoxia- and glutamine deprivation-induced autophagy in cancer cells.

Conclusions:

  • PGK1-mediated phosphorylation of BECN1 represents a critical regulatory step in controlling autophagy under specific stress conditions relevant to the tumor microenvironment.
  • This finding offers a potential therapeutic target for modulating autophagy in cancer treatment.
Keywords:
BECN1PGK1autophagycancerglutaminestress

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