Downregulation of SPARC Expression Decreases Cell Migration and Invasion Involving Epithelial-Mesenchymal Transition through the p-FAK/p-ERK Pathway in Esophageal Squamous Cell Carcinoma

Purpose: Secreted protein acidic and rich in cysteine (SPARC) is an extracellular glycoprotein overexpressed in various malignancies, including esophageal squamous cell carcinoma (ESCC), and is involved in tumor development and progression. This study was initially designed to investigate the biological roles of SPARC in ESCC cell lines by silencing SPARC expression. Methods: The expression of SPARC was examined in eight human ESCC cell lines. Eca109 and HKESC cell lines with high SPARC expression were selected and transiently transfected with SPARC-targeted small interfering RNAs (siRNAs) and subsequently evaluated its impact on cell proliferation, migration and invasion in vitro, as well as the underlying mechanism. Results: Knockdown of SPARC by the specified siRNAs in Eca109 and HKESC cell lines resulted in dramatically downregulation of SPARC expression, and significantly decreased cell migration and invasion involving epithelial-mesenchymal transition (EMT) in vitro. Moreover, SPARC-targeted siRNA reduced the activation of phosphorylated focal adhesion kinase (p-FAK) and extracellular regulated protein kinase (p-ERK). Furthermore, downregulation of either FAK or SPARC expression with specified siRNAs inhibited the phosphorylation of ERK and inhibited cell migration and invasion. However, decreased SPARC expression showed no impact on cell proliferation, survival or apoptosis of Eca109 and HKESC cells when comparing to control transfected groups. Conclusions: These results demonstrated that downregulation of SPARC could decrease cell migration and invasion involving EMT via the p-FAK/p-ERK pathway that might serve as a novel therapeutic target against ESCC.