Defects in Autophagy Lead to Tumor Development

When the cellular self-digestive process of autophagy is defective, waste products--including toxic peptides--accumulate, leading to disease syndromes such as Alzheimer's and Parkinson's disease as well as increased likelihood for tumor development.

Investigators from Rutgers University (Piscataway, NJ, USA) employed mouse models as well as tissue samples from human liver, lung, and kidney tumors to study the molecular causes of defective autophagy. They reported in the June 12, 2009, online edition of the journal Cell that tumor cells have sustained expression of the p62 protein, a protein that is normally destroyed in normal cells during the autophagic process.

The p62 protein is known to be a significant contributor to several metabolic pathways that lead to metabolic syndrome, Alzheimer's disease, and other related diseases. The absence of the p62 protein has a profound effect on the accumulation of tau protein, amyloid beta protein, and an increase in blood insulin levels.

The current study is one of the first to relate p62 to cancer and tumor development. "This discovery is important, because we now have an opportunity to look at people at risk for cancer before it develops,” said senior author Dr. Eileen White, professor of molecular biology and biochemistry at Rutgers University. "These latest findings show that p62 can act as a marker to identify certain cancers and that we can manipulate p62 levels to stimulate the process of autophagy and ultimately tumor suppression.”

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