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Promise and Progress - How Cancer Cells Keep Going When Other Cells Stop

Promise & Progress - A Spectrum of Achievements

How Cancer Cells Keep Going When Other Cells Stop

Date: January 15, 2015

Proceedings of the National Academy of Sciences, July 28, 2014

Researchers have uncovered another way that cancer cells subvert normal cellular processes to maintain their unchecked growth.  Most normal cells do not divide unless there is enough oxygen around to support additional cells, but many cancer cells continue to divide even when oxygen is in short supply.

Two decades ago, Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of pediatrics, medicine, oncology, radiation oncology, biological chemistry and genetic medicine, discovered HIF-1alpha, a protein that accumulates when cells are deprived of oxygen and that stimulates the formation of new blood vessels that deliver the oxygen and nutrients that cells need to survive.  Since more cells require more oxygen, HIF-1alpha also blocks cell division by preventing cells from replicating their DNA. Cancer cells want HIF-1alpha around to stimulate blood vessel growth—except when they want to divide.

How do cancer cells accomplish these seemingly incompatible tasks? Maimon Hubbi, Ph.D., a postdoctoral researcher in Semenza’s lab, found that cancer cells use two proteins that have long been known to control cell growth. Cdk2, a protein that suddenly appears just before cells begin to replicate their DNA, attaches to HIF-1alpha and causes its destruction. Once cells finish replicating their DNA, Cdk2 is itself destroyed and replaced by Cdk1, which also attaches itself to HIF-1alpha but has the opposite effect: Cdk1 protects HIF-1alpha from destruction and increases its ability to stimulate blood vessel growth.  Several drugs that inactivate Cdk1—and cause HIF-1alpha destruction—are currently being tested as anti-cancer agents in clinical trials.

The research was funded by the National Cancer Institute and the American Cancer Society.

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