Previous cell biological studies demonstrate that the actin bundling protein fascin1 regulates cell motility, migration and invasion. Human studies demonstrate that fascin1 is upregulated in many epithelial cancers. This review gives a brief overview of the role of fascin1 in cell migration and invasion, but focuses mainly on the regulation and clinical relevance of fascin1 in epithelial cancers. Here, we propose fascin1 as a potent prognostic biomarker for breast, colorectal, esophageal cancers and head and neck squamous cell carcinomas. Fascin1 may also be an attractive drug target against these carcinomas in the future, but more studies are needed.Epithelial cancers (carcinomas) comprise 80-90% cancer types. Although early tumor diagnosis and improved multimodality therapy have helped to reduce the mortality of cancer patients, prognosis remains poor if the cancer is invasive and metastatic. Fascin was first discovered as a 55 kDa actinassociated protein in the filopodia of coelomocytes in sea urchin. 1 Fascin has three isoforms in mammals: fascin1, which is widely expressed, fascin2, which is expressed in retina and ear hair cells and fascin3 which is specific to testis. 2 In adult mammals, fascin1 is expressed mainly in neuronal cells, 3,4 endothelial cells, 5 fibroblasts, 6 smooth muscle cells, 7 dendritic cells 8 and some motile embryonic cells (neuroblasts 9 and melanoblasts 10 ). In normal epithelial tissue, fascin1 is absent or present at low levels. However, fascin1 is frequently upregulated when epithelial tissues become malignant. [11][12][13] This review focuses on the recent advances in the regulation of fascin1 in cancer and summarizes the existing clinical studies in various types of cancers to reveal its prognostic significance. Recent literature suggests that the cell migration promoting protein fascin1 could serve as a prognostic marker in multiple types of carcinomas, including breast, colorectal, esophageal cancers and head and neck squamous cell carcinomas (HNSCC).
Actin Bundling Protein Fascin1: A Key Player in Cell Migration and InvasionFascin exists in equilibrium between the cytoplasm and the cytoskeleton and its association with actin filaments is enhanced by interaction with specific matrix 14 or stimulation of cells with growth factors or cytokines. 15 Fascin1 has at least two binding sites for actin filaments, so it crosslinks them into tightly packed parallel bundles, oriented with their growing ends toward the plasma membrane. Migration is driven by a combination of actin polymerization dynamics underneath the plasma membrane, adhesion to the substratum and contractile forces generated by actin-myosin structures. Fascin is found in actin-rich cytoskeletal structures, such as stress fibers, 16,17 protrusive membrane structures (microspikes and filopodia 18 ) and degradative structures (invadopodia 19,20 and podosome 7 ) (Fig. 1a) which are all pro-migratory. Previous cell biological studies have revealed that fascin1 executes key roles in these structures and that cells expressi...