Abstract
BackgroundSwitch-associated protein 70 (SWAP-70) is a guanine nucleotide exchange factor that is involved in cytoskeletal rearrangement and regulation of migration and invasion of malignant tumors. However, the mechanism by which SWAP-70 regulates the migration and invasion of glioblastoma (GB) cells has not been fully elucidated.MethodsThis study used an online database to analyze the relationship between SWAP-70 expression and prognosis in GB patients. The in vitro wound healing assay and transwell invasion assay were used to determine the role of SWAP-70 in GB cell migration and invasion as well as the underlying mechanism.ResultsWe found that patients with high SWAP-70 expression in the GB had a poor prognosis. Downregulation of SWAP-70 inhibited GB cell migration and invasion, whereas SWAP-70 overexpression had an opposite effect. Interestingly, SWAP-70 expression was positively correlated with the expression of the standard form of CD44 (CD44s) in GB tissues. Downregulation of SWAP-70 also reduced CD44s protein expression, whereas SWAP-70 overexpression enhanced CD44s protein expression. However, downregulation of SWAP-70 expression did not affect the mRNA expression of CD44s. Reversal experiments showed that overexpressing CD44s in cell lines with downregulated SWAP-70 partially abolished the inhibitory effects of downregulated SWAP-70 on GB cell migration and invasion.ConclusionsThese results suggest that SWAP-70 may promote GB cell migration and invasion by regulating the expression of CD44s. SWAP-70 may serve as a new biomarker and a potential therapeutic target for GB.
Highlights
Switch-associated protein 70 (SWAP-70) is a guanine nucleotide exchange factor that is involved in cytoskeletal rearrangement and regulation of migration and invasion of malignant tumors
We found that SWAP70 regulated the expression of the standard form of CD44 (CD44s) to promote GB cellular migration and invasion
Further analysis of the relationship between SWAP-70 expression and the prognosis of glioma patients using online TCGA and GEO databases showed that patients with high SWAP-70
Summary
Switch-associated protein 70 (SWAP-70) is a guanine nucleotide exchange factor that is involved in cytoskeletal rearrangement and regulation of migration and invasion of malignant tumors. The mechanism by which SWAP-70 regulates the migration and invasion of glioblastoma (GB) cells has not been fully elucidated. Glioblastoma (GB) is the most common and malignant type of brain tumor in adults. The molecular mechanisms underlying the high migration and invasion of GB have not been fully elucidated. Shi et al Cancer Cell Int (2019) 19:305 environment and intracellular responses, the processes of which dynamically regulate actin filaments, microtubules, and intermediate filaments [8, 9]. Previous studies have shown that filaments that present inside pseudopods and membranous folds are associated with and are regulated by switch-associated protein 70 (SWAP-70) [10, 11]. It has been shown that deletion of SWAP-70 in mouse embryonic fibroblasts results in impaired membrane wrinkles, suggesting that SWAP-70 plays a crucial role in the formation of the membranous cellular folds [13, 14]
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