Cold Spring Harbor Laboratory scientists trace a novel way cells are disrupted in cancer

A splicing factor targets known cancer-related proteins

A research team at Cold Spring Harbor Laboratory (CSHL) is clarifying a previously unappreciated way that cellular processes are disrupted in cancer.

Last year, scientists from the same CHSL team discovered that a "splicing factor" called SF2/ASF--a protein that changes the instructions for how other proteins are assembled--can induce tumors in cell cultures. The team's newly published results show that, in ways not yet fully understood, this same splicing factor acts on a group of other molecules that has long been known to affect cancer.

A Cascade of Molecular Interactions Leading to Cancer

Understanding such complex molecular interactions may one day lead to new approaches to cancer treatment. Cancers are enormously complex, and eventually, in most instances, they find ways of disrupting a large fraction of cellular processes. To untangle and reverse the changes, researchers seek to identify sequences of events in which molecules each affect one another in turn, ultimately inducing cancer-cell behavior.

For example, one protein may affect another by chemically disabling it, or by slowing the gene expression that produces it from the "instructions" contained in DNA. A drug that blocks any step in such a "pathway" has a chance to slow or prevent the disease.

Until recently, however, cancer researchers have paid scant attention to factors that affect others through "alternative splicing," a mechanism that changes how DNA instructions are cut and pasted together at the level of RNA intermediaries to form final templates for the production of proteins.

"Splicing is a critical step in gene expression," said Adrian R. Krainer, Ph.D., a CSHL professor who is an expert on RNA splicing. "Like other steps in gene expression, it seems to malfunction in cancer." Last year, Krainer and his colleagues found that several known splicing factors are present at higher-than-normal levels in some tumors. For example, a factor known as SF2/ASF was elevated in more than 20% of lung and colon tumors. Moreover, laboratory cultures of mouse or rat cells developed characteristics of tumors when they were programmed to make higher-than-normal levels of this splicing factor.