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Abstract
Fascin-1 is a filamentous actin-binding protein that crosslinks actin microfilaments into tight, parallel bundles. These bundles are important for the extension of microspikes, filopodia and invadopodia from cell surfaces and for the functionality of these protrusions in cell migration and/or dynamic sensing of the local microenvironment. Fascin-1 is absent in normal colonic epithelium, but its upregulation in colorectal adenomas and adenocarcinomas and its correlation with an aggressive clinical course has piqued the interest of many laboratories with research interests in cancer metastasis. This report summarizes current knowledge of the molecular interactions of fascin-1 in relation to its activities and mechanisms of upregulation in colorectal carcinoma cells. The status and key questions surrounding investigations of fascin-1 as a novel, early prognostic biomarker in colorectal cancer are discussed. Ongoing pre-clinical research into new migration inhibitory and anti-metastatic compounds that alter the actin cytoskeleton, and the goal of targeting fascin-1, is also discussed.
Acknowledgement
Apologies to those whose work is not cited directly, due to length restrictions.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.
No writing assistance was utilized in the production of this manuscript.
Fascin-1 is an actin-bundling protein that is not present in most adult epithelia, but is upregulated in the most clinically aggressive carcinomas.
In colorectal cancer, fascin-1 is present in around 16% of adenomas and 25% of adenocarcinomas and correlates with increased risk of mortality, disease progression and metastasis.
Fascin-1 functions in the organization of parallel actin-bundles that are found in cell surface microspikes, filopodia and invadopodia. It also contributes to focal adhesion dynamics and can be a component of stress fibers.
By participating in these structures, fascin-1 in colon carcinoma cells acts to promote cell migration. Mouse xenograft models show that fascin-1 can promote primary tumor development and metastasis.
Additional binding partners of fascin-1 include conventional protein kinase C and Lin-11/Isl-1/Mec-3 kinase 1 and 2.
Transcriptional upregulation of fascin-1 in colon carcinoma cells involves transcription factors cAMP response element-binding protein and aryl hydrocarbon receptor; also downregulation of miRNA-145.
Approaches to target either the fascin-1 transcript or protein are under early pre-clinical investigation.