Abstract
Fascin-1 (FSCN1) is an actin-bundling protein that induces cell membrane protrusions, increases cell motility, and is overexpressed in various human epithelial cancers, including esophageal squamous cell carcinoma (ESCC). We analyzed various protein-protein interactions (PPI) of differentially-expressed genes (DEGs), in fascin knockdown ESCC cells, to explore the role of fascin overexpression. The node-degree distributions indicated these PPI sub-networks to be characterized as scale-free. Subcellular localization analysis revealed DEGs to interact with other proteins directly or indirectly, distributed in multiple layers of extracellular membrane-cytoskeleton/ cytoplasm-nucleus. The functional annotation map revealed hundreds of significant gene ontology (GO) terms, especially those associated with cytoskeleton organization of FSCN1. The Random Walk with Restart algorithm was applied to identify the prioritizations of these DEGs when considering their relationship with FSCN1. These analyses based on PPI network have greatly expanded our comprehension of the mRNA expression profile following fascin knockdown to future examine the roles and mechanisms of fascin action.
Highlights
Fascin-1 (FSCN1) is an actin-bundling protein that induces cell membrane protrusions and increases cell motility (Hashimoto 2011; Tan et al, 2013)
We demonstrated that fascin becomes overexpressed in the malignant transformation of normal esophageal squamous cells to cancer cells (Rong et al, 2004), and upregulation of fascin is markedly correlated with cell proliferation and lymph node metastasis, suggesting fascin could be a potential novel biomarker for esophageal squamous cell carcinoma (ESCC) (Zhang et al, 2006). shRNA-mediated knockdown of fascin in ESCC cells decreases cell proliferation, cell invasiveness and tumor growth in vivo, suggesting fascin plays crucial roles in regulating neoplastic progression
These three sub-networks indicated that knockdown of fascin greatly altered the protein-protein interactions (PPI) network in ESCC, as hundreds of differentially-expressed genes (DEGs) interact with thousands of proteins to enlarge the biological consequences of fascin knockdown
Summary
Fascin-1 (FSCN1) is an actin-bundling protein that induces cell membrane protrusions and increases cell motility (Hashimoto 2011; Tan et al, 2013). Accumulated evidence shows fascin is overexpressed in several human epithelial cancers, such as gastric, colonic, skin, breast, and urothelial cancers (Tan et al, 2013). Overexpression of fascin in these tumors usually correlates with highgrade, extensive invasion, distant metastasis, or poor prognosis, serving as a biomarker for various aggressive carcinomas. We demonstrated that fascin becomes overexpressed in the malignant transformation of normal esophageal squamous cells to cancer cells (Rong et al, 2004), and upregulation of fascin is markedly correlated with cell proliferation and lymph node metastasis, suggesting fascin could be a potential novel biomarker for esophageal squamous cell carcinoma (ESCC) (Zhang et al, 2006). Affymetrix GeneChip Human genome U133 plus 2.0 arrays has been applied to analyze the mRNA expression profile in ESCC cells stably expressing fascin shRNA (Xie et al, 2010)
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