TSRI scientists awarded NIH grant to investigate molecular machinery involved in cancer metastasis

Cancer metastasis occurs when tumor cells escape from a primary tumor, via the blood stream, and establish tumors in secondary locations. When the metastases are found in distant tissues and organs, doctors call this stage IV cancer, and the survival rate is low.

Now scientists at The Scripps Research Institute (TSRI) have been awarded a grant of more than $1.8 million from the National Institutes of Health's National Cancer Institute to investigate the molecular machinery involved in metastasis. This basic research could one day point to new approaches to help patients.

"We think we'll be able to relate specific molecules on the tumor cell surface and irreversible modifications of these molecules to patient outcomes," said TSRI Professor James Quigley, who will co-direct the five-year project with TSRI Assistant Professor Elena Deryugina.

The researchers will focus on transmembrane proteins, which carry signals from outside a tumor cell to the cell's interior. In a previous study, the researchers found that the body's enzymes outside tumor cells can cut—or "cleave"—a cancer-related transmembrane protein called CDCP1. Instead of deterring the cancer, the cleavage appeared to make CDCP1 signals even stronger, supporting survival of tumor cells in the blood stream and their metastasis throughout the body.

"We also found that if you block cleavage or make CDCP1 non-cleavable, you could dampen the level of metastasis," said Deryugina, underlining the potential clinical significance of the work.

With the new grant, the researchers will investigate the nature of the cleaving enzymes and whether cleavage changes signaling in other transmembrane proteins involved in tumor cell survival and metastasis.

The researchers will also analyze cancer patient data provided by the University of California, San Diego to explore links between cleaved proteins and patient survival.