MadSci Network: Cell Biology

Re: What changes occur in the cytoskeleton that lead to malignancy?

Date: Sun Dec 9 18:28:22 2007
Posted By: William Gunn, Grad student, The Center for Gene Therapy, Tulane University
Area of science: Cell Biology
ID: 1194112133.Cb

Thanks for your question, julz. I'm sorry it's has taken me a couple days to get to your question, but I think I have a good answer for you.

The main link between cytoskeletal changes and cancer is the APC protein. Loss of APC has been said to result in cancer by many different mechanisms such as failure to properly segregate chromosomes, failure to undergo apoptosis, and deregulated beta-catenin signaling.

Peter Duesberg is a leading proponent of the idea that chromosome instability(aneuploidy) leads to cancer, as opposed to the other way around. The basic idea is that aneuploidy leads to thousands of genes being turned on or off inappropriately, or present in higher or lower amounts than normal, because upon division, a cell might get both of some chromosomes, leaving the other cell with none. When this happens in a tissue, most of the resulting cells will die, but some cells will end up with a combination of genes such as growth factors being expressed while not expressing some others such as those needed for apoptosis. These cells then are able to divide rapidly without responding to the normal signals your body uses to keep cell division in check. Duesberg has some other crazy ideas that I do not agree with, but I tend to think he's at least partially right about the role of chromosome stability in cancer.

There's also evidence that loss of APC can result directly in loss of apoptosis, and it's well known that mutation of APC can destroy its ability to bind beta-catenin, which promotes cell division. Roel Nusse has a page with more information about the role of beta-catenin in cancer.

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