Adhesion, Contractility Enable Metastatic Cells to go Against the Grain

Bioengineers at the University of California San Diego and San Diego State University have discovered a key feature that allows cancer cells to break from typical cell behavior and migrate away from the stiffer tissue in a tumor, shedding light on the process of metastasis and offering possible new targets for cancer therapies. It has been well documented that cells typically migrate away from softer tissue to stiffer regions within the extracellular matrix — a process called durotaxis. Metastatic cancer cells are the rare exception to this rule, moving away from the stiffer tumor tissue to softer tissue, and spreading the cancer as they migrate. What enables these cells to display this atypical behavior, called adurotaxis, and migrate away from the stiffer tumor hasn't been well understood. Building off previous research led by bioengineers in UC San Diego Professor Adam Engler's lab, which found that weakly adherent, or less sticky, cells migrated and invaded other tissues more than strongly adherent cells, the team has now shown that the contractility of these weakly adherent cells is what enables them to move to less stiff tissue. By chemically reducing the contractility of weakly adherent cells, they become durotactic, migrating toward stiffer tissue; increasing the contractility of strongly adherent cells makes them migrate down the stiffness gradient. The researchers reported their findings on March 9 in .