In early test tube and mouse studies, investigators at Johns Hopkins Medicine and the Johns Hopkins Kimmel Cancer Center have found that nonmuscle myosin IIC (MYH14), a protein activated in response to mechanical stress, helps promote metastatic behavior in pancreatic cancer cells, and that the compound 4-hydroxyacetophenone (4-HAP), known to stiffen myosin IIC-containing cells, can send it into overdrive, overwhelming the ability of cells to invade nearby tissue.
In early test tube and mouse studies, investigators at Johns Hopkins Medicine and the Johns Hopkins Kimmel Cancer Center have found that nonmuscle myosin IIC (MYH14), a protein activated in response to mechanical stress, helps promote metastatic behavior in pancreatic cancer cells, and that the compound 4-hydroxyacetophenone (4-HAP), known to stiffen myosin IIC-containing cells, can send it into overdrive, overwhelming the ability of cells to invade nearby tissue.
The work, described online in July in the journal Cancer Research, found that 4-HAP reduced metastatic tumor formation in a mouse model of human pancreatic cancer by assessing the fraction of liver surface covered by tumor tissue. The researchers say their results suggest that targeting MYH14 and similar cytoskeletal proteins with 4-HAP is a potentially novel strategy for improving the survival of pancreatic cancer patients, and could eventually become part of a combination strategy with chemotherapy and/or immunotherapy agents.
Much of the focus in developing new cancer drugs involves trying to inhibit a process or protein of interest, says senior study author Douglas N. Robinson, Ph.D., a professor of cell biology and oncology at Johns Hopkins. But some nonmuscle myosin II proteins have tumor-suppressive activities, so inhibiting them could increase rather than decrease the likelihood of metastasis.
“There are two basic ways to stop the runaway train that is cancer metastasis. One is to throw up a roadblock in front of it, like an inhibitor. Or, we can get behind the train and push it faster and shove it off the tracks, and that’s kind of what we’re doing with 4-HAP,” he says. “We’re taking the system and shoving it to the right instead of the left, and thereby helping to halt the progression of disease-like behavior, such as invasion and metastasis.”
Read more at Johns Hopkins Medicine
Photo Credit: PDPics via Pixabay
