Fascin is a protein that organizes the internal framework of cells. It specializes in bundling long, thin protein strands called actin filaments. These bundled actin filaments contribute to a cell’s strength, shape, and internal organization, which are fundamental for many basic cellular processes.
The Cellular Architect: Fascin’s Role in Healthy Cells
In healthy cells, fascin is a key protein for creating and maintaining cellular structures. It bundles actin filaments into rigid, rod-like projections called filopodia, which extend from the cell surface. These dynamic, finger-like protrusions allow cells to explore their environment, sense surroundings, and interact with other cells or surfaces.
Filopodia are also important for cell movement, such as when immune cells navigate tissues to reach infection sites. Fascin also contributes to cell adhesion, enabling cells to stick to each other or to the extracellular matrix. Additionally, fascin is involved in nerve cell development, required for the proper extension and branching of axons, which transmit electrical signals.
Fascin’s ability to tightly bundle actin filaments provides the stiffness needed for filopodia to push against membranes and drive cell movement. This precise regulation of fascin’s activity is essential for the controlled migration and structural integrity of healthy cells.
Fascin’s Role in Cancer Metastasis
While fascin serves normal functions in healthy cells, many aggressive cancer cells produce it in unusually high amounts. This overexpression is frequently observed across various cancer types, including breast, colorectal, pancreatic, lung, liver, and prostate cancers. Elevated fascin levels are consistently associated with a less favorable prognosis and increased metastatic progression.
Cancer cells exploit fascin’s function to become highly mobile and invasive. Increased fascin in these cells leads to more numerous and robust filopodia and invadopodia. These specialized protrusions help cancer cells break through tissue barriers, allowing them to detach from the primary tumor and invade surrounding healthy tissues.
This enhanced mobility enables cancer cells to travel through the bloodstream or lymphatic system, a process called dissemination. In distant locations, fascin aids their ability to exit blood vessels and infiltrate new organs, forming secondary tumors, known as metastatic colonization. Fascin promotes this spread, but not the initial development of cancer.
Beyond its role in cell movement, fascin is implicated in other aspects of cancer progression. It contributes to cancer cells’ ability to resist anoikis, a programmed cell death that occurs when cells detach from their usual environment. Fascin can also play a part in chemotherapy resistance and the self-renewal capacity of cancer stem-like cells, supporting the disease’s spread and persistence.
Targeting Fascin for Medical Treatment
The strong association of high fascin levels with cancer metastasis and poorer patient outcomes has made it a focus of medical research. Fascin can be used as a prognostic marker. Clinicians can measure fascin levels in tumor tissue to predict how aggressive a cancer might be and its likelihood of spreading. For example, increased fascin expression correlates with disease progression and shorter survival in oral squamous cell carcinoma patients.
Another avenue is developing therapeutic strategies that directly target fascin. Scientists are working on fascin inhibitors, drugs designed to block the protein’s activity. These inhibitors interfere with fascin’s ability to bind to actin filaments, preventing the formation of actin bundles that cancer cells rely on for movement. By disrupting these structures, fascin inhibitors can reduce tumor cell motility and invasiveness.
Studies in mouse models show that inhibiting fascin can reduce tumor cell migration and metastasis. Specific fascin inhibitors have decreased metastasized tumor cells in the lungs and slowed metastatic relapse in some breast cancer models. This suggests that targeting fascin could be a viable approach to preventing or slowing cancer spread.
Fascin’s Involvement Beyond Cancer
Fascin’s role in cell structure and movement extends its relevance beyond cancer, impacting other biological contexts. Some viruses, for example, exploit fascin-driven machinery to facilitate their spread. Human T-lymphotropic virus type 1 (HTLV-1) and Epstein-Barr virus (EBV) induce fascin expression through specific cellular pathways, promoting cell-to-cell transmission and enabling infected cells to become more invasive.
Fascin also shows involvement in certain inflammatory disorders. Research indicates fascin is overexpressed in inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s colitis. Fascin expression levels often correlate with disease severity. Fascin is found in areas of mucosal regeneration and at the edges of ulcers, suggesting it may play a role in tissue repair processes within the inflamed gut.