p62 degradation by autophagy: another way for cancer cells to survive under hypoxia

Autophagy. 2009 Apr;5(3):410-2. doi: 10.4161/auto.5.3.7823. Epub 2009 Apr 16.


Hypoxia is a common feature of advanced solid tumors causing cancer progression and resistance to treatment. Hypoxia activates mitophagy as well as macroautophagy that regulates carcinoma cell survival. p62/SQSTM1, a multifunctional protein that targets proteins to degradation by proteasomes and autophagy, is itself downregulated by hypoxia-activated autophagy in carcinoma cells. The hypoxic degradation of p62 is seen across several carcinoma cell lines. In contrast to hypoxic activation of mitochondrial autophagy, the hypoxia-induced degradation of p62 occurs partially independently from the HIF pathway. The finding argues that in addition to transcriptional gene regulation through HIF, autophagy has a central role in the regulation of hypoxic cancer cell survival responses.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Autophagy / physiology*
  • Cell Hypoxia
  • Cell Nucleus / metabolism
  • Cell Survival
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • Hypoxia*
  • Mitochondria / metabolism
  • Models, Biological
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Phosphorylation
  • Sequestosome-1 Protein
  • Signal Transduction


  • Adaptor Proteins, Signal Transducing
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Extracellular Signal-Regulated MAP Kinases