A University of Colorado Cancer Center review published in the journal Brain Research provides an overview of TAM family cell signaling in the central nervous system, and specifically within the cancer gioblastoma multiforme.
“Our group and many others around the country and the world have been working to discover targeted treatments for cancer. Successfully targeting TAM proteins could be a major advance in treating this aggressive brain cancer,” says Angela Pierce, PhD, investigator at the CU Cancer Center and research associate at Children’s Hospital Colorado.
The TAM family of cell surface receptors is made up of the three proteins Tyro3, Axl and MerTK. Think of these cell surface receptors as the retractable tentacles of a sea anemone. When the “tentacle” of a cell-surface receptor grabs a specific particle, it can retract, bringing the information of that particle inside the cell. Inside the cell, this information can control the behavior of the cell’s DNA. These cell surface proteins, technically called “receptor tyrosine kinases” or RTKs, are essential for cell communication: when an RTK is activated, it in turn activates a cell’s machinery to enable survival, proliferation, or migration.
In the case of many cancers, malfunctioning RTKs signal the cell to survive, proliferate or migrate inappropriately. For example, the cells of glioblastoma multiforme overexpress MerTK, while normal brain tissue does not. The difference may provide treatment options for this most common and least treatable childhood brain cancer.
“We thought it was time to see if RTKs in general, or the TAM family or even more specifically MerTK does the same thing in glioblastoma multiforme that it appears to do in some other cancer types,” Pierce says.
Specifically, Pierce points out TAM family signaling isn’t unique to cancer and that inhibiting any link in the chain of cell signaling may lead to consequences in addition to the desired result.
“This is a brain we’re talking about,” Pierce says. “And TAM family signaling is involved in things like synapse function in addition to driving the growth of cancer.”
The group’s review collects existing thought demonstrating the importance of TAM family signaling in the cells of the brain and adds to the increasing evidence that MerTK is a driver and valid target in glioblastoma.