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. 2019 Nov 21:19:305.
doi: 10.1186/s12935-019-1035-3. eCollection 2019.

SWAP-70 promotes glioblastoma cellular migration and invasion by regulating the expression of CD44s

Lin Shi #  1 , Huize Liu #  1 , Yifeng Wang #  1 , Yulong Chong  1   2 , Jie Wang  1 , Guanzheng Liu  1 , Xu Zhang  3 , Xiangyu Chen  1 , Huan Li  1 , Mingshan Niu  1   4 , Jun Liang  3 , Rutong Yu #  1   3 , Xuejiao Liu #  1   3
Affiliations

SWAP-70 promotes glioblastoma cellular migration and invasion by regulating the expression of CD44s

Lin Shi et al. Cancer Cell Int. .

Abstract

Background: 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. However, the mechanism by which SWAP-70 regulates the migration and invasion of glioblastoma (GB) cells has not been fully elucidated.

Methods: This 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.

Results: We 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.

Conclusions: These 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.

Keywords: CD44s; Glioblastoma; Invasion; Migration; SWAP-70.

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Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
High expression of SWAP-70 correlates with poor outcomes in glioblastoma patients. a SWAP-70 expression in non-tumor brain tissues and glioma tissues measured by Western blotting. b Kaplan–Meier survival analysis of glioma patients using the Gene Expression Omnibus dataset. Among the 273 glioma cases, 144 tissues had high SWAP-70 expression. c Overall survival analysis of glioblastoma patients using The Cancer Genome Atlas glioblastoma dataset
Fig. 2
Fig. 2
Downregulation of SWAP-70 inhibits glioblastoma cellular migration and invasion. a Downregulation efficiency of SWAP-70 in U251 and U87 cells validated by Western blotting. b, c Migratory abilities of U251 and U87 cells after downregulating SWAP-70 expression detected with the in vitro scratch assay. The number of migrated cells was counted. d, e Invasive abilities of U251 and U87 cells after downregulating SWAP-70 expression assessed with the transwell invasion assay. The number of invading cells was counted. All data are expressed as the mean ± SEM (n = 3 per group; *P < 0.05)
Fig. 3
Fig. 3
SWAP-70 overexpression promotes glioblastoma cellular migration and invasion. a Overexpression efficiency of SWAP-70 in U251 and U87 cells verified by Western blotting. b, c Migratory abilities of U251 and U87 cells after overexpressing SWAP-70 determined with the in vitro scratch assay. d, e Invasive abilities of U251 and U87 cells after overexpression of SWAP-70 measured with the transwell invasion assay. f–i Quantitative analysis of the numbers of invading and migrating cells compared with those of the control group. All data are presented as the mean ± SEM (n = 3 per group; *P < 0.05)
Fig. 4
Fig. 4
SWAP-70 regulates the expression of CD44s in glioblastoma cells. a Correlation analysis of SWAP-70 and CD44s expression in glioblastoma tissues. b, c Effects of downregulated or overexpressed SWAP-70 on CD44s protein expression analyzed by Western blotting. d, e Effects of downregulated or overexpressing CD44s on SWAP-70 protein expression assessed by Western blotting. f Effects of downregulated SWAP-70 on CD44s mRNA expression determined by semi-quantitative PCR. g Relative mRNA expression of CD44s in cells with stable SWAP-70 downregulation measured by quantitative PCR
Fig. 5
Fig. 5
CD44s overexpression partially reverses the inhibitory effect of downregulated SWAP-70 on glioblastoma cellular migration and invasion. a Transient transfection of the CD44s-overexpression plasmid in U251 cells with stable SWAP-70 downregulation. Transfection efficiency and protein expression of SWAP-70 and CD44s were assessed by Western blotting. b Statistical analysis of SWAP-70 and CD44s protein levels. c Effect of CD44s overexpression on the migratory ability of glioblastoma cells after downregulating SWAP-70 determined with the in vitro scratch assay. d Effect of CD44s overexpression on the invasive ability of glioblastoma cells after downregulating SWAP-70 analyzed with the transwell invasion assay. e Statistical analysis of the numbers of migrating and invading cells. All data are presented as the mean ± SEM (n = 3 per group; *P < 0.05)
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