The Fatal Flip: How Nerve Cells go from Healthy to Cancerous

Every gene in the human genome has a job to do. One such gene, called Merlin, prevents cells from dividing out of control and forming into tumors. A so-called ‘tumor suppressor,’ Merlin has proven to be essential to maintaining healthy cell division. Scientists knew that without Merlin, nerve cells grew uncontrollably, often leading to tumors and a type of inherited cancer called neurofibromatosis type 2 (NF2).

Scientists have uncovered the mechanism whereby an absence of the gene called Merlin causes normal nerve cells to turn rogue.

Scientists have uncovered the mechanism whereby an absence of the gene called Merlin causes normal nerve cells to turn rogue.

Now, scientists have uncovered the mechanism that causes an absence of Merlin to transform nerve cells into rogue, tumor-producing cells—helping shed new light on how the smallest genetic shifts—even in just one gene—can have an impact on the normal pattern of growth and development of cells.

Reporting in the latest issue of Cancer Cell, a joint team from the Sloan-Kettering Institute for Cancer Research and Plymouth University Peninsula Schools of Medicine and Dentistry have found that without Merlin a chemical pathway, called the Hippo pathway, switches on. This, in turn, spurs tumor cell growth in nerve cells.

Professor Dr. Oliver Hanemann of Plymouth University and one of the study’s senior authors, explained in a July 22 news release:

“We have known for some time that the loss of the tumor suppressor Merlin resulted in the development of nervous system tumors, and we have come tantalizingly close to understanding how this occurs.”

This research advance is especially important in the case of NF2, a condition for which there are limited treatment options. Current treatments usually involve a combination of surgery and radiation, but rarely is the cancer fully eradicated.

“By understanding the mechanism [of Merlin], we can use this knowledge to develop effective drug therapies—in some cases adapting existing drugs—to treat patients for whom current therapies are limited and potentially devastating.”

Stem cell biology has also proven essential when shining a light on or explaining the complexities surrounding cancer’s underlying mechanisms, including the notion of cancer stem cells—a concept that has gained increasing support in recent years. To learn more about how CIRM-funded scientists are harnessing stem cells to understand—and develop treatments for—cancer, check out our 2009 Spotlight on Cancer Stem Cells as well as our Brain Tumor fact sheet.

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