Fascin is an actin-bundling protein. FSCN1 is recognized as a candidate biomarker for multiple cancer types and as a potential therapeutic target. Now, a new study by researchers at King’s College London, Ghent University, and AstraZeneca demonstrates that fascin is transported into the nucleus of cancer cells where it plays a role in cell motility and growth.

The study, “Nuclear fascin regulates cancer cell survival,” is published in the journal eLife.

“Fascin is an important regulator of F-actin bundling leading to enhanced filopodia assembly,” wrote the researchers. “Fascin is also overexpressed in most solid tumors where it supports invasion through control of F-actin structures at the periphery and nuclear envelope. Recently, fascin has been identified in the nucleus of a broad range of cell types but the contributions of nuclear fascin to cancer cell behavior remain unknown. Here, we demonstrate that fascin bundles F-actin within the nucleus to support chromatin organization and efficient DDR.”

“We have previously shown that fascin resides in the control center of the cell—the nucleus —at certain times in the cell’s growth cycle,” explained lead author Campbell Lawson, PhD, research associate at the Randall Centre for Cell and Molecular Biophysics, King’s College London. “However, it was not known how fascin’s movement or function within the nucleus are controlled, and this hinders our ability to develop treatments that block its role in promoting cancer growth and spread.”

The team of researchers created a series of cancer cell lines with and without functional fascin, as well as a suite of fascin “nanobodies” labeled with fluorescent markers.

The researchers observed that fascin is actively transported in and out of the nucleus and, once there, it supports the assembly of actin bundles. Fascin also interacted with another group of important proteins in the cell nucleus, called histones. When fascin is not involved in bundling actin, it is bound to histone H3—an important player involved in organizing DNA within the nucleus.

The researchers looked further into the interaction between fascin and histones by observing whether fascin was also involved in DNA repair processes in cancer cells. They found DNA repair was impaired in cells lacking fascin, indicating that the protein might be required for cancer cells to trigger their response to DNA damage caused by chemo- or radiotherapy.

“Our study provides insights into a new role for fascin in controlling nuclear actin bundling to support tumor cell viability,” concluded senior author Maddy Parsons, PhD, professor of cell biology at the Randall Centre for Cell and Molecular Biophysics, King’s College London. “Given fascin is at very high levels in many solid tumors, but not in normal tissues, this molecule is an interesting therapeutic target. We propose that promoting fascin accumulation in the nucleus of cancer cells, rather than only focusing on targeting it in the cell cytoplasm, could be an alternative approach that would prevent both tumor growth and spread.”

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