Allows cancer cells to divide even when oxygen-starved
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 lysosomes have been implicated in a cell’s division decisions.
Remarkably, in certain cancer cells, 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 oxygen levels. 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.
Gregg Semenza is the C. Michael Armstrong Professor of Medicine and a professor of pediatrics, oncology, radiation oncology and biological chemistry at the Johns Hopkins University School of Medicine. Other authors of the report include Maimon Hubbi, Daniele Gilkes, Hongxia Hu and Ishrat Ahmed of the Johns Hopkins University School of Medicine; and Kshitiz of Yale University.
This work was supported by grants from the National Cancer Institute (K99CA181352) and the American Cancer Society.
Catherine Kolf | newswise
Insect Antibiotic Provides New Way to Eliminate Bacteria
15.11.2018 | Universität Zürich
New findings help to better calculate the oceans’ contribution to climate regulation
15.11.2018 | Jacobs University Bremen gGmbH
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure
Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...
Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly
The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...
09.11.2018 | Event News
06.11.2018 | Event News
23.10.2018 | Event News
15.11.2018 | Information Technology
15.11.2018 | Life Sciences
15.11.2018 | Life Sciences