Knockdown of Slit2 promotes growth and motility in gastric cancer cells via activation of AKT/β-catenin

  • Authors:
    • Rongliang Shi
    • Zhen Yang
    • Weiyan Liu
    • Bingya Liu
    • Ziping Xu
    • Ziping Zhang
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  • Published online on: December 2, 2013     https://doi.org/10.3892/or.2013.2887
  • Pages: 812-818
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Abstract

We previously showed that Slit2 was highly expressed in gastric cancer tissues that exhibit less advanced clinicopathological features, suggesting a tumor suppressor role for Slit2. In the present study, we investigated the effects of Slit2 knockdown on gastric cancer cells. Slit2-specific shRNAs were used to generate Slit2-knockdown SGC-7901 gastric cancer cells. Cell proliferation assay, Annexin V/PI double staining and cell cycle analysis were used to investigate the role of Slit2 knockdown in cell growth. Wound-healing and in vitro migration/invasion assays were performed. Subcutaneous tumor formation and peritoneal spreading in nude mice were employed to examine the in vivo effects of Slit2 knockdown. Cell signaling changes induced by Slit2 knockdown were analyzed by immunoblotting. Slit2 knockdown increased gastric cancer cell growth in monolayer and soft agar/Matrigel 3D culture. Slit2 knockdown inhibited apoptosis but did not alter cell cycle progression. Slit2-knockdown cells formed larger tumors and produced more peritoneal metastatic nodules in nude mice. Slit2 knockdown increased AKT phosphorylation, activated anti-apoptotic signaling, suppressed GSK3β activity and induced β-catenin activation. Blocking the effects of PI3K/AKT using pharmacological inhibitors abolished the ability of Slit2 knockdown to induce apoptosis resistance and cell migration/invasion. These results indicate that Slit2 knockdown promotes gastric cancer growth and metastasis through activation of the AKT/β‑catenin-mediated signaling pathway.
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2014-February
Volume 31 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Shi R, Yang Z, Liu W, Liu B, Xu Z and Zhang Z: Knockdown of Slit2 promotes growth and motility in gastric cancer cells via activation of AKT/β-catenin. Oncol Rep 31: 812-818, 2014
APA
Shi, R., Yang, Z., Liu, W., Liu, B., Xu, Z., & Zhang, Z. (2014). Knockdown of Slit2 promotes growth and motility in gastric cancer cells via activation of AKT/β-catenin. Oncology Reports, 31, 812-818. https://doi.org/10.3892/or.2013.2887
MLA
Shi, R., Yang, Z., Liu, W., Liu, B., Xu, Z., Zhang, Z."Knockdown of Slit2 promotes growth and motility in gastric cancer cells via activation of AKT/β-catenin". Oncology Reports 31.2 (2014): 812-818.
Chicago
Shi, R., Yang, Z., Liu, W., Liu, B., Xu, Z., Zhang, Z."Knockdown of Slit2 promotes growth and motility in gastric cancer cells via activation of AKT/β-catenin". Oncology Reports 31, no. 2 (2014): 812-818. https://doi.org/10.3892/or.2013.2887