Open Access

AREG mediates the epithelial‑mesenchymal transition in pancreatic cancer cells via the EGFR/ERK/NF‑κB signalling pathway

  • Authors:
    • Li Wang
    • Lili Wang
    • Hui Zhang
    • Junliang Lu
    • Zhiwen Zhang
    • Huanwen Wu
    • Zhiyong Liang
  • View Affiliations

  • Published online on: February 27, 2020     https://doi.org/10.3892/or.2020.7523
  • Pages: 1558-1568
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Amphiregulin (AREG) is a member of the epidermal growth factor (EGF) family and is expressed in a plethora of cancers. The biological roles of AREG in the regulation of the epithelial‑mesenchymal transition (EMT) in pancreatic cancer remain unclear. To investigate the expression of epidermal growth factor receptor (EGFR) and AREG in pancreatic cancer cell lines, RT‑qPCR, western blot analysis, and ELISA were performed. RNAi and exogenous AREG treatment were used to alter AREG expression. Wound‑healing and Transwell assays were performed to evaluate cell migration and invasion abilities. Western blot analysis and immunofluorescence staining were utilized to detect the expression of EMT markers. The protein expression of potential key factors involved in EMT, as well as those of the ERK, AKT, STAT3 and NF‑κB pathways, were analysed by western blotting. The role of AREG in tumour growth in vivo was further determined using an orthotopic model of pancreatic cancer. Knockdown of AREG inhibited AsPC‑1 cell migration and invasion. AREG knockdown upregulated E‑cadherin but downregulated vimentin, Snail and Slug expression in AsPC‑1 cells. In addition, AREG stimulation increased cell migration, invasion and EMT in PANC‑1 cells, and an NF‑κB inhibitor decreased AREG‑induced cell migration, invasion and EMT in PANC‑1 cells. AREG stimulation increased the nuclear accumulation of NF‑κB through the EGFR/ERK signalling pathway to induce EMT. Tumour growth and metastasis were decreased by AREG silencing in an orthotopic model of pancreatic cancer. AREG may play a critical role in cell migration, invasion, and EMT by activating the EGFR/ERK/NF‑κB signalling pathway in pancreatic cancer cells.

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May 2020
Volume 43 Issue 5

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

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APA
Wang, L., Wang, L., Zhang, H., Lu, J., Zhang, Z., Wu, H., & Liang, Z. (2020). AREG mediates the epithelial‑mesenchymal transition in pancreatic cancer cells via the EGFR/ERK/NF‑κB signalling pathway. Oncology Reports, 43, 1558-1568. https://doi.org/10.3892/or.2020.7523
MLA
Wang, L., Wang, L., Zhang, H., Lu, J., Zhang, Z., Wu, H., Liang, Z."AREG mediates the epithelial‑mesenchymal transition in pancreatic cancer cells via the EGFR/ERK/NF‑κB signalling pathway". Oncology Reports 43.5 (2020): 1558-1568.
Chicago
Wang, L., Wang, L., Zhang, H., Lu, J., Zhang, Z., Wu, H., Liang, Z."AREG mediates the epithelial‑mesenchymal transition in pancreatic cancer cells via the EGFR/ERK/NF‑κB signalling pathway". Oncology Reports 43, no. 5 (2020): 1558-1568. https://doi.org/10.3892/or.2020.7523