When cancer cells spread from the primary tumor, they typically enter a long-term dormant state before multiplying to form metastatic tumors. Researchers had a hunch that epigenetic and chromatin remodeling mechanisms helped maintain this state of dormancy. A prime suspect was the histone-protein variant macroH2A2, since its expression is lost or weakened at different stages of cancer progression, particularly in metastasis. But how macroH2A2 contributes to cancer-cell dormancy was unclear.

In a study that published online on December 2 in Science Advances, co-corresponding author Julio Aguirre-Ghiso, Ph.D., and colleagues describe the mechanism by which macroH2A2 appears to suppress metastasis. In research involving animal models and disseminated cancer cells (DCCs, i.e., cancer cells that have left the primary tumor) from patients with head-and-neck cancer, the researchers found that macroH2A2 limits metastatic growth by activating transcriptional programs associated with both cell quiescence and senescence. The researchers were able to keep DCCs that had spread to the lungs of mice in a stable state of dormancy by restoring macroH2A2 function, suggesting a possible strategy for preventing or suppressing metastasis.

Dr. Aguirre-Ghiso is the Rose C. Falkenstein Chair in Cancer Research, professor of cell biology, of medicine, and of oncology, director of the Cancer Dormancy and Tumor Microenvironment Institute at Montefiore Einstein Cancer Center, and co-director of the Gruss-Lipper Biophotonics Center at Einstein.