Autophagy, p62, and prostate cancer

According to a report today on, there are suggestions that defective  “autophagy” — the process through which a cell “self-digests” because of the action of enzymes originating within the same cell — may be crucial to the amount and aggressiveness of at least some cancers. Prostate cancer may be one of those types of cancer.

The report is based on an article by Mathew et al. in this week’s issue of the journal Cell. It is supported by a mini-review (by Jorge Moscat and Diaz-Meco) of the mechanism of action of the p62 enzyme (also known as sequestosome-1), which appears to be a critical enzyme in tumor growth and development.

What Mathew et al. have done is to show that elimination of the p62 enzyme by autophagy seems to effectively slow down or shut down the process of tumor growth (“tumorigenesis”). These discoveries suggest that the amount of p62 in any specific cell is a central player in the life and death decisions of that cell. Cancer cells with defective autophagy will accumulate high levels of p62 and will therefore be more capable of tumorigenesis, whereas cancer cells with lower levels of p62 (because they have normal autophagy processes) will be far less capable of tumorigenesis.

According to one of the study authors, about 50 percent of patients with prostate cancer have defective autophagy.

Under normal circumstances, p62 is associated with the “cleaning up” of toxic materials in cells. To use an analogy developed by the research team — p62 is like  “the garbageman” and is normally responsible for the regular removal of “the garbage” that accumulates in any specific cell. However, when the process of cell autophagy breaks down, not only does the amount of garbage start to accumulate but so does the number of garbagemen too. In  order to stop the growth of cancer, you have to be able to clean out both the garbage and the surfeit of garbagemen too!

Clearly this is an interesting new hypothesis that may lead to new drugs that could act both therapeutically to treat cancer and preventively to stop the development of the disease, but it will likely be years before we can tell how accurately this hypothesis reflects the actual processes of autophagy and control over the levels of p62, let alone whether drugs can actually be developed that will work specifically to treat or prevent prostate cancer.

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