Newly indentified protein linked to cancer cell survival

A team of Vanderbilt-Ingram Cancer Center investigators have identified a new secreted protein and its receptors that appear to give a cancer cell the ability to fuel its own growth and present a potential target for anti-cancer drugs.

Secreted proteins are released from one cell to transmit a signal to another cell instructing a particular behavior such as cell growth, migration or survival. These proteins cannot act alone; they must act through a receptor or receptors on the receiving cell, so discovery of the receptor is also important.

Initially called MOB-5, this new protein has been renamed Interleukin 24 (IL-24), with the approval of the Human Genome Nomenclature Committee, because the investigators work demonstrates relationship to the family of proteins known as interleukins. These proteins are typically secreted by immune system cells in response to a triggering event, such as injury or infection. However, the Vanderbilt-Ingram team has found IL-24 and two receptors expressed in colon cancer cells, making it the first interleukin to be found along with its receptors in tumor cells.

"There is an old saying that cancer is like a wound that never heals," said Peng Liang, Ph.D., associate professor of Cancer Biology, whose laboratory did the work reported this month in the Journal of Biological Chemistry. "This gives credence to that old saying."

Using a process called differential display to compare gene expression between cancer and normal cells, the team found this gene to be expressed only in tumor cells and particularly those in which the oncogene (cancer-causing gene) RAS is activated. RAS is mutated frequently in colon and pancreas cancers, among others, and it appears from this groups work that RAS activation leads to unregulated expression of IL-24 and its receptors.

"At the time, we didnt know it was an interleukin, just that it was a secreted protein," Liang said. "Finding the difference between tumor and normal cells is

Contact: Cynthia Manley
Vanderbilt University Medical Center

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