Scientists Awarded $2 Million to Study Tumor-Inhibiting Proteins

By Eric Sauter

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have been awarded just over $2 million from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health to identify proteins that play key roles in tumor cell proliferation and to determine if targeting these proteins could result in the inhibition of tumor growth.

Joseph Kissil, a TSRI associate professor, is the principal investigator for the five-year study.

While normal cells possess mechanisms that inhibit rapid growth, tumor cells find ways to continue their expansion. Signals to grow or stop growing are triggered by a number of conditions, including what is known as “cell-cell contact” when cells reach critical density. The new study is focused on finding out exactly how this cell-cell contact controls growth.

“A lot of things go wrong in cancer, and one of them is known as ‘loss of contact inhibition,’” Kissil said. “Normally, cells know to stop proliferating when they get signals from the environment. In cancer, these mechanisms become dysfunctional and that leads to accelerated tumor growth.”

A central player in regulating these signals is a protein named merlin, a product of a tumor suppressor gene NF2 (neurofibromatosis type 2); neurofibromatosis is a disease caused by genetic mutations that result in tumors of the nervous system. The NF2 gene also stops functioning in a broad range of tumors, when merlin then becomes incapacitated.

Kissil and his colleagues recently identified proteins known as angiomotins, which are involved in cell movement and new blood-vessel growth, as holding sway over merlin’s ability to inhibit tumor cells.

“Angiomotins give us a handle on understanding the process,” Kissil said. “This project could be a first step in identifying potential therapeutics that can attack tumor cell growth at its source.”

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