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California researchers have developed a method to help control the number of nuclear pores in cells. This capacity should provide valuable information to help with cancer treatment.
If you consider the cell nucleus as a DNA bank, nuclear pores are the security gates around its perimeter. However, more safety doors are not necessarily desirable, as evidenced by the fact that some cancer cells contain a considerable excess of nuclear pores.
Scientists at the Salk Institute report that they have developed a way to manipulate the number of individual nuclear pores – a breakthrough that they hope will one day prevent cancer cells from proliferating out of control.
Commenting on the value of this new capacity, lead author Martin HetzerSalk, vice president and chief of the science bureau, said: "Previously, we did not have the tools to artificially increase the nuclear pores.
Our study provides an experimental track to ask critical questions: What are the consequences of increasing the number of nuclear pores in a healthy cell to mimic those found in a cancer cell? Does this affect the activity of genes? Why do cancer cells increase the number of nuclear pores?
Nuclear pores are essential characteristics of all cells that provide a controlled way to move cellular material inside and outside a nucleus. In organisms ranging from fungi to mammals, individual cells have these transport channels that carry a thousand events per second. Individual nuclear pores are made from multiple copies of proteins called nucleoporins. Hetzer and his colleagues studied the nucleoporin Tpr, implicated in some cancers.
The team has shown, for the first time, that each of the transport channels in a cell is unique and that each cell nucleus has a specific number of nuclear pores. Then, the team used molecular methods to remove the Tpr in order to observe its effect on the number of nuclear pores, with a surprising result.
"Generally, when you" cut down "or remove some of the proteins that make up the nuclear pore complex, the total number of nuclear pores decreases," says Asako McCloskey, first author of the newspaper and research associate Salk.
"Our surprising discovery was that when we get rid of the nucleoporin Tpr, the number of nuclear pore has increased dramatically."
"It's the first time that changing a component in the transport channel has been shown to increase the number of nuclear pores," adds Hetzer. This indicates that Tpr plays a role not in the transport itself, but in regulating the assembly of nuclear pores. Knowledge could be crucial for future attempts to manipulate the number of nuclear pores to treat diseases. For example, cells with higher metabolic activity, such as stimulated thyroid follicular cells or aggressive tumors, have more nuclear pores per nucleus.
Other research has shown that preventing the transport of cancer-related "cargo" proteins through nuclear pores can have dramatic effects on cancer treatment. Targeting nuclear pores could also negate the resistance of aggressive cancers to multiple drugs, with a higher number of nuclear pores in tumor cells allowing them to export chemotherapy out of the nuclei.
Then, the lab will use the new technique to identify the effects of changing nuclear pore numbers in various cell types.
This research was reported in the journal Genes & Development.
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