Breast Cancer Breakthrough: A 'Toggle Switch' That Controls Metastasis and Growth

Breast cancer ribbon, stethoscopeBreast cancer is the second most commonly diagnosed cancer in women in the U.S. Fortunately, though, the disease is also better understood than even a few years ago, and, as a result, is now less lethal.
In an important new study, researchers identified a molecular “toggle switch” that controls whether a breast cancer cell is more likely to metastasize, spreading to a new part of the body, or to stay in place and proliferate more rapidly.
“This could be a marker to determine whether or not the breast cancer is likely to metastasize or not,” says Professor Susan Rotenberg (GC/Queens College; Biochemistry, Biology, Chemistry). Rotenberg is an author on the study, published in Cellular Signalling.
Knowing which is more likely to happen could help doctors determine a patient’s prognosis or treatment plan, as metastasis makes a patient’s cancer more difficult to control and treat.
Cells contain structures called microtubules, which are involved in cell movement and proliferation. One of the building blocks of a microtubule is a protein called alpha-tubulin. There is a specific site on each alpha-tubulin, named serine-165, that is involved in this toggle switch. Whether this site is phosphorylated or not — in other words, whether an enzyme adds a small molecule containing a phosphorus atom to the site — is what causes the switch to flip.
If alpha-tubulin is phosphorylated at this site, the cell’s potential for metastasis increases, and it proliferates in the breast more gradually. But if the enzyme does not add a phosphoryl molecule to the site, the cell is more likely to stay where it is and multiply, causing the tumor to grow.
The scientists also analyzed a database of DNA from breast cancer patients’ primary tumors. They found that some tumor cells contained mutations in alpha-tubulin that block phosphorylation, making the cell less likely to metastasize. Another type of mutation at the site chemically mimicked the effect of phosphorylation, raising the cell’s potential for metastasis. This discovery could have clinical applications.
“You could use genomics to analyze the DNA of the patient’s tumor, and see if there is a mutation there, and what type of mutation it is” Rotenberg says.
While further research is needed to confirm that these mutations are common enough to be clinically useful, the study also gives researchers a better understanding of enzyme signaling pathways in breast cells.
“There is a lot to learn here about the basic science,” Rotenberg says.

Submitted on: FEB 15, 2019

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