A key step in metastasis requires cancer cells to squeeze through extremely small gaps in the endothelium to enter and exit the vasculature. This requires the cell’s nucleus to be compressed to ~10% of its size. During metastatic transformation, the cell nucleus changes from a rigid structure, like a tiny golf ball, to a ‘squishier’ structure, like a water balloon, to allow the cells to enter the bloodstream and metastasize. Dr. James Holaska’s research program at Rowan University is interested in the mechanisms that drive these nuclear changes.
The objective of Dr. Holaska’s studies was to establish how emerin regulates nuclear structure during cancer transformation to drive cell migration, invasion, and metastasis. Dr. Holaska found invasive breast cancer cells had reduced emerin expression and had smaller, misshapen nuclei. Expression of emerin in invasive breast cancer cells increased their nuclear size, blocked their migration through small pores, and inhibited metastasis in orthotopic mouse models of breast cancer. Dr. Holaska’s results suggest emerin acts through stabilizing the nucleoskeleton to maintain nuclear architecture.
This W. W. Smith Charitable Trust grant allowed Dr. Holaska to embark on this new field of study for which he has made important, potentially paradigm-shifting findings. This discovery and exploration of this new paradigm will stimulate new areas of research in metastasis. Discoveries directly or indirectly relating to this work will identify new targets for therapeutic development.
James M. Holaska, Ph.D., Rowan University, focuses on emerin, an inner nuclear membrane protein, to study how nuclear changes drive cell migration, invasion, and metastasis. W. W. Smith Charitable Trust Research Project: “Emerin Regulation of Nuclear Architecture During Cell Invasion and Metastasis”