PMID- 32323797
OWN - NLM
STAT- MEDLINE
DCOM- 20210205
LR  - 20211027
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 43
IP  - 5
DP  - 2020 May
TI  - AREG mediates the epithelial‑mesenchymal transition in pancreatic cancer cells 
      via the EGFR/ERK/NF‑kappaB signalling pathway.
PG  - 1558-1568
LID - 10.3892/or.2020.7523 [doi]
AB  - 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‑kappaB 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‑kappaB inhibitor decreased AREG‑induced cell migration, invasion and EMT in PANC‑1 
      cells. AREG stimulation increased the nuclear accumulation of NF‑kappaB 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‑kappaB signalling pathway in pancreatic cancer cells.
FAU - Wang, Li
AU  - Wang L
AD  - Department of Pathology, Peking Union Medical College Hospital, Research Center 
      for Molecular Pathology, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100730, P.R. China.
FAU - Wang, Lili
AU  - Wang L
AD  - Department of Pathology, Peking Union Medical College Hospital, Research Center 
      for Molecular Pathology, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100730, P.R. China.
FAU - Zhang, Hui
AU  - Zhang H
AD  - Department of Pathology, Peking Union Medical College Hospital, Research Center 
      for Molecular Pathology, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100730, P.R. China.
FAU - Lu, Junliang
AU  - Lu J
AD  - Department of Pathology, Peking Union Medical College Hospital, Research Center 
      for Molecular Pathology, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100730, P.R. China.
FAU - Zhang, Zhiwen
AU  - Zhang Z
AD  - Department of Pathology, Peking Union Medical College Hospital, Research Center 
      for Molecular Pathology, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100730, P.R. China.
FAU - Wu, Huanwen
AU  - Wu H
AD  - Department of Pathology, Peking Union Medical College Hospital, Research Center 
      for Molecular Pathology, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100730, P.R. China.
FAU - Liang, Zhiyong
AU  - Liang Z
AD  - Department of Pathology, Peking Union Medical College Hospital, Research Center 
      for Molecular Pathology, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100730, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20200227
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Amphiregulin/*genetics/*metabolism
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Epithelial-Mesenchymal Transition
MH  - ErbB Receptors/genetics/metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mice
MH  - NF-kappa B/metabolism
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - Neoplasm Transplantation
MH  - Pancreatic Neoplasms/genetics/metabolism/*pathology
MH  - Signal Transduction
MH  - Up-Regulation
PMC - PMC7107775
OTO - NOTNLM
OT  - AREG
OT  - pancreatic cancer
OT  - EMT
OT  - ERK
OT  - NF-kappaB
EDAT- 2020/04/24 06:00
MHDA- 2021/02/07 06:00
PMCR- 2020/02/27
CRDT- 2020/04/24 06:00
PHST- 2019/08/11 00:00 [received]
PHST- 2020/01/21 00:00 [accepted]
PHST- 2020/04/24 06:00 [pubmed]
PHST- 2021/02/07 06:00 [medline]
PHST- 2020/04/24 06:00 [entrez]
PHST- 2020/02/27 00:00 [pmc-release]
AID - or-43-05-1558 [pii]
AID - 10.3892/or.2020.7523 [doi]
PST - ppublish
SO  - Oncol Rep. 2020 May;43(5):1558-1568. doi: 10.3892/or.2020.7523. Epub 2020 Feb 27.