Salk: “Tweaking cells’ gatekeepers could lead to new way to fight cancer”

NOMIS scientist Martin Hetzer and other Salk Institute researchers have devised a way to manipulate numbers of individual nuclear pores — a breakthrough that may one day stop cancerous cells from proliferating out of control. The finding was published in an article in the journal Genes & Development.

Nuclear pores are essential elements of all cells that provide controlled ways to move cellular material in and out of a nucleus. In organisms ranging from fungi to mammals, individual cells possess these transport channels that mediate a thousand events per second. Individual nuclear pores are fashioned from multiple copies of 30 proteins known as nucleoporins. Hetzer and colleagues looked at the nucleoporin Tpr, which has been implicated in certain cancers.

The team showed that each of the transport channels within a cell is unique, and each cell nucleus possesses a specific number of nuclear pores. Next, the team used molecular methods to remove Tpr to see its effect on the number of nuclear pores, with a surprising result. Cells with the Tpr protein have fewer nuclear pores than cells without the protein. Typically, removing proteins in the nuclear pore complex results in a reduction of nuclear pores. This indicates that Tpr plays a role not in transport itself, but in regulating the assembly of nuclear pores. These new insights could be crucial for future attempts to manipulate numbers of nuclear pores to treat disease.

Hetzer is Salk’s vice president and chief science officer, as well as a NOMIS board member. The Salk Institute has been a NOMIS partner since 2008.

Photo: Salk Institute