Protein type could offer clue in cancer spread

In 2001, James Holaska, Ph.D., started his postdoctoral fellowship in a lab that studied protein interactions in the nucleus of a cell and was introduced to the protein, emerin. 

“There was nothing known about it and I thought it was an exciting place to start. I found that very invigorating and exciting—uncharted territory—I was told to catch the wave and ride it,” Holaska said. 

With support from the National Institutes of Health, the New Jersey Commission on Cancer Research and prior funding from the W.W. Smith Charitable Trust, Holaska’s lab studies emerin and the role it plays in cancer metastasis and muscle disease.

“Emerin is expressed everywhere in the body, but it only affects skeletal, muscle and heart cells,” said Holaska, a professor of biomedical sciences at Cooper Medical School of Rowan University. “As far as we know, mutations in emerin have nothing to do with the person’s overall health outside of these tissues. We want to know what emerin is doing. The goal is, if we can identify what is going wrong, we can develop therapies to treat it."

“On the cancer side of things, it is understood that emerin helps maintain the structure of a cell. It keeps the center part of the cell, the nucleus, strong—encased like a golf ball with a really hard shell on the outside.” 

To spread to other parts of the body, Holaska explained, cancer cells must leave the primary tumor site, traveling through small slits like pores into the bloodstream, which requires the nucleus to become more like a water balloon than a golf ball. In metastasized breast cancer, for example, this process could lead to a new tumor in another site, such as the brain, Holaska explained.

“We know that emerin is expressed 50% less in triple-negative breast cancer cells, leading to increased metastasis,” he said. The idea is then, if a patient with breast cancer shows a loss of emerin, clinicians could monitor a patient more closely for early signs of metastasis. However, more research is needed to demonstrate loss of emerin as a potent biomarker for increased metastasis. 

“More research is also needed to understand how emerin strengthens the nucleus to block cancer spread. We can then use that information as a target for the development of therapeutics,” Holaska said. “If you can identify what is wrong, maybe you can develop therapies to target it, so you can fix it.”

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