Open Access

Girdin interaction with vimentin induces EMT and promotes the growth and metastasis of pancreatic ductal adenocarcinoma

  • Authors:
    • Wulin Wang
    • Hao Chen
    • Wenjie Gao
    • Sheng Wang
    • Kai Wu
    • Chen Lu
    • Xiagang Luo
    • Lianhong Li
    • Chunzhao Yu
  • View Affiliations

  • Published online on: May 19, 2020     https://doi.org/10.3892/or.2020.7615
  • Pages: 637-649
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer of the digestive tract that has a high potential for metastasis and a poor prognosis. Girdin was first reported in 2005 as an actin‑binding protein and was designated as Akt‑phosphorylation enhancer (APE); thus, Girdin has been revealed to have an important role in regulating cancer development. There is additional evidence indicating that Girdin is associated with cell proliferation, migration, invasion and survival in certain cancers. However, the potential mechanisms involving Girdin and mobility in pancreatic cancer have not been elucidated. In the present study, it was revealed that Girdin was highly expressed in pancreatic cancer tissue and was associated with tumor grade. The present study, to the best of our knowledge, is the first aimed at investigating the unknown role of Girdin in PDAC metastasis. A short hairpin RNA for Girdin (sh‑Girdin) was successfully constructed with recombinant adenoviral vectors to suppress the expression of Girdin in pancreatic cancer cell lines (PANC‑1 and BXPC‑3). The silencing efficiency of the Girdin shRNA was determined by RT‑qPCR and western blot analysis, and decreased Girdin expression in the cytoplasm was revealed by immunofluorescence detection. Then, sulforhodamine B (SRB) and colony formation assays were used to confirm that the knockdown of Girdin inhibited proliferation in vitro, and Transwell assays were used to examine the influence of Girdin knockdown on cellular mobility. Animal experiments also confirmed that silencing the expression of Girdin in pancreatic cancer cells inhibited the growth and metastasis of pancreatic cancer in vivo. Transforming growth factor‑β (TGF‑β) is a common inducer of epithelial‑mesenchymal transition (EMT) and can effectively induce EMT in PDAC. Notably, TGF‑β‑treated cells exhibited changes in the classic biological markers of EMT. The expression of E‑cadherin, a marker of the epithelial phenotype, increased, and the expression of N‑cadherin and vimentin, markers of the interstitial phenotype, decreased in response to sh‑Girdin. According to these experiments, Girdin may affect pancreatic cancer progression and development by interacting with vimentin. Therefore, there is evidence indicating that Girdin could be designated as a prognostic biological indicator and a candidate therapeutic target for pancreatic cancer.

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August-2020
Volume 44 Issue 2

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

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APA
Wang, W., Chen, H., Gao, W., Wang, S., Wu, K., Lu, C. ... Yu, C. (2020). Girdin interaction with vimentin induces EMT and promotes the growth and metastasis of pancreatic ductal adenocarcinoma. Oncology Reports, 44, 637-649. https://doi.org/10.3892/or.2020.7615
MLA
Wang, W., Chen, H., Gao, W., Wang, S., Wu, K., Lu, C., Luo, X., Li, L., Yu, C."Girdin interaction with vimentin induces EMT and promotes the growth and metastasis of pancreatic ductal adenocarcinoma". Oncology Reports 44.2 (2020): 637-649.
Chicago
Wang, W., Chen, H., Gao, W., Wang, S., Wu, K., Lu, C., Luo, X., Li, L., Yu, C."Girdin interaction with vimentin induces EMT and promotes the growth and metastasis of pancreatic ductal adenocarcinoma". Oncology Reports 44, no. 2 (2020): 637-649. https://doi.org/10.3892/or.2020.7615