Study: Key Cancer Target Could Halt Cancer Spread

Researchers have shown that a protein called fascin is transported into the nucleus of cancer cells where it plays an important role in cell motility and growth
Fascin is actively transported in and out of the nucleus and, once there, it supports the assembly of actin bundles (Unsplash)
Fascin is actively transported in and out of the nucleus and, once there, it supports the assembly of actin bundles (Unsplash)

The study reveals an important route through which fascin promotes cancer development and provides insights into potential pathways that could block its action.

Fascin is known to control the structures that allow cells to move – specifically the assembly of bundles of a protein called actin, which create the tiny ‘legs’ that cancer cells use to migrate to distant sites within the body. Fascin is also known to be at much higher levels in most solid tumours, where it helps cancer cells migrate and invade into other tissues. This invasion - or ‘metastasis’ - of tumour cells is the main reason why many cancers are so hard to treat

Fascin is actively transported in and out of the nucleus and, once there, it supports the assembly of actin bundles (Unsplash)
Study: AI may help in predicting Recurrence of Colorectal Cancer

To understand fascin further, the team created a series of cancer cell lines with and without functional fascin, as well as a suite of fascin ‘nanobodies’ labelled with fluorescent markers, to alter its location in cells and explore its interactions with other proteins in the nucleus.

They found that fascin is actively transported in and out of the nucleus and, once there, it supports the assembly of actin bundles. Indeed, cells without fascin were unable to build nuclear actin bundles to the same extent. 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 organising DNA within the nucleus.

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 (Unsplash)
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 (Unsplash)

Given the interaction of fascin with histones, the team looked at whether fascin was also involved in DNA repair processes in cancer cells, which helps them to survive. 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. Fascin-depleted cells also had changes to their chromatin structure – the way the DNA is packaged in the cell – compared to cells with normal fascin levels.

Fascin is actively transported in and out of the nucleus and, once there, it supports the assembly of actin bundles (Unsplash)
Cancer diagnostics and screening use Smart Contact Lenses
Nuclear fascin plays an important role in nuclear actin assembly, DNA structure and repair (Unsplash)
Nuclear fascin plays an important role in nuclear actin assembly, DNA structure and repair (Unsplash)

Although nuclear fascin plays an important role in nuclear actin assembly, DNA structure and repair, it is also important in the cell cytoplasm, where it helps cancer cells build tiny appendages called filopodia, which promote invasion. So the team wanted to understand whether moving all fascin into the nucleus would prevent the cytoplasmic function of fascin. As they anticipated, in cells with enhanced nuclear fascin, the number of filopodia was significantly reduced because there was no fascin in the cytoplasm to support assembly of these structures.

The cells also invaded less into 3-dimensional scaffolds that mimic the tissue surrounding tumours. Importantly, cells that had forced nuclear fascin had significantly reduced growth rates and viability because they assembled large stable actin bundles in the nucleus which prevented them from going through the cell cycle. Collectively, these results indicate that, rather than trying to find ways to block fascin, forcing it all into the nucleus of cancer cells could prevent their growth and movement. (NS/Newswise)

Related Stories

No stories found.
Medbound
www.medboundtimes.com