Cell's recycling center implicated in division decisions

July 28, 2014

Most cells do not divide unless there is enough oxygen present to support their offspring, but certain cancer cells and other cell types circumvent this rule. Researchers at The Johns Hopkins University have now identified a mechanism that overrides the cells' warning signals, enabling cancers to continue to divide even without a robust blood supply. In the process, the researchers found that lysosomes—the cell's protein "recycling centers"—help govern cell division decisions. They also uncovered new evidence that certain drugs can halt the growth of tumors that have high levels of the protein HIF-1alpha.

A summary of their findings will be published the week of July 28 in the journal PNAS.

Low levels of oxygen stimulate the production and activation of HIF-1alpha, which protects cells in two ways. Primarily, it turns on several genes for proteins that help the cells adapt to the lack of oxygen. It can also stop the duplication of DNA, which prevents cells from dividing and adding more oxygen-using cells to an already harsh environment.

Knowing that some cells ignore the warnings of HIF-1alpha and divide anyway, Gregg Semenza, M.D., Ph.D., and his team looked for interactions between HIF-1alpha and Cdk1 and Cdk2, proteins known to regulate cell division decisions. They found that HIF-1alpha interacts with both of them, but that Cdk1 increases HIF-1alpha levels, while Cdk2 lowers them.

Semenza's team suspected that Cdk1 and Cdk2 were acting on HIF-1alpha by marking or not marking it for destruction by the cell's miniature "garbage disposals," called proteasomes. But when the researchers blocked proteasome function, they found no changes in HIF-1alpha levels. Instead, Cdk1 and Cdk2 turned out to alter HIF-1alpha levels by marking or not marking it for destruction by the cell's lysosomes. To their knowledge, this is the first time have been implicated in a cell's division decisions.

Remarkably, in certain , Cdk2 was able to decrease levels of HIF-1alpha while also stimulating its gene activation activity. The net effect was that cells continued dividing while coping with low . In cultured cells, drugs that inhibit Cdk1 prevented HIF-1alpha levels from falling and restored its ability to halt cell division, suggesting they may be effective treatments for certain cancers.

Explore further: Understanding cancer energetics

More information: PNAS DOI: 10.1073/pnas.1412840111

Related Stories

Understanding cancer energetics

June 4, 2011

(Medical Xpress) -- It's long been known that cancer cells eat a lot of sugar to stay alive. In fact, where normal, noncancerous cells generate energy from using some sugar and a lot of oxygen, cancerous cells use virtually ...

Researchers link cell division and oxygen levels

June 11, 2011

Cells grow abundant when oxygen is available, and generally stop when it is scarce. Although this seems straightforward, no direct link ever has been established between the cellular machinery that senses oxygen and that ...

Recommended for you

Researchers thwart cancer cells by triggering 'virus alert'

August 27, 2015

Working with human cancer cell lines and mice, researchers at the Johns Hopkins Kimmel Cancer Center and elsewhere have found a way to trigger a type of immune system "virus alert" that may one day boost cancer patients' ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.