Researchers collaborating from St. Anna Children's Cancer Research Institute Vienna, King's College London, Institute Curie Paris, and ETH Zürich in Basel have described the mechanism by which cancer cells break free from crowded environments. Their new research is published in the journal Science.
The researchers found that cells are able to sense environmental compression and use their nuclei to trigger responses to crowding that allow for sufficient ‘personal space’. They do so through a process of nuclear membrane stretching by way of a protein called Ca2+-dependent phospholipase or cPLA2.
And this is where the findings become relevant, explain the authors.
Lead author Alexis Lomakin, PhD, says that cPLA2 is a target for cancer drug development. "Pharmaceutical companies are currently testing small molecule inhibitors of cPLA2. Based on our data, downregulating the activity of cPLA2 in tumor cells might interfere with their ability to escape the primary tumor and metastasize to distant locations.”
The researchers will continue to test various hypotheses in order to determine how nuclear deformation could be related to metastatic potential and resistance to chemotherapy and immunotherapy.
"We are very excited about what comes next," says Dr. Lomakin. "For many years, pathologists have been evaluating changes in the shape of the nucleus to discriminate between different stages of tumor growth; however, how these structural-mechanical alterations of the nucleus functionally impact cancer cells remained completely unexplored."