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Netrin-1 suppresses the MEK/ERK pathway and ITGB4 in pancreatic cancer.

The axon guidance factor netrin-1 promotes tumorigenesis in multiple types of cancers, particularly at their advanced stages. Here, we investigate whether netrin-1 is involved in the in vivo growth of pancreatic adenocarcinoma. We show that netrin-1 is significantly under-expressed in stage-I/II pan... Full description

Journal Title: Oncotarget April 26, 2016, Vol.7(17), pp.24719-24733
Main Author: An, Xi-Zhou
Other Authors: Zhao, Zhi-Guo , Luo, Yu-Xuan , Zhang, Ran , Tang, Xiao-Qiang , Hao, De- Long , Zhao, Xiang , Lv, Xiang , Liu, De- Pei
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1949-2553 ; DOI: 10.18632/oncotarget.8348
Link: http://search.proquest.com/docview/1808376301/?pq-origsite=primo
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recordid: proquest1808376301
title: Netrin-1 suppresses the MEK/ERK pathway and ITGB4 in pancreatic cancer.
format: Article
creator:
  • An, Xi-Zhou
  • Zhao, Zhi-Guo
  • Luo, Yu-Xuan
  • Zhang, Ran
  • Tang, Xiao-Qiang
  • Hao, De- Long
  • Zhao, Xiang
  • Lv, Xiang
  • Liu, De- Pei
subjects:
  • Animals–Genetics
  • Carcinoma, Pancreatic Ductal–Metabolism
  • Cell Line, Tumor–Pathology
  • Cell Proliferation–Physiology
  • Chick Embryo–Genetics
  • Extracellular Signal-Regulated MAP Kinases–Metabolism
  • Hek293 Cells–Metabolism
  • Heterografts–Genetics
  • Humans–Metabolism
  • Integrin Beta4–Genetics
  • MAP Kinase Signaling System–Metabolism
  • Mice–Pathology
  • Netrin-1–Pathology
  • Pancreatic Neoplasms–Pathology
  • Integrin Beta4
  • Netrin-1
  • Extracellular Signal-Regulated MAP Kinases
  • Mek/Erk
  • Pp2a
  • Integrin-Beta4
  • Netrin-1
  • Pancreatic Ductal Adenocarcinoma
ispartof: Oncotarget, April 26, 2016, Vol.7(17), pp.24719-24733
description: The axon guidance factor netrin-1 promotes tumorigenesis in multiple types of cancers, particularly at their advanced stages. Here, we investigate whether netrin-1 is involved in the in vivo growth of pancreatic adenocarcinoma. We show that netrin-1 is significantly under-expressed in stage-I/II pancreatic ductal adenocarcinoma (PDAC). Netrin-1 over-expression effectively arrests the growth of xenografted PDAC cells without decreasing cell proliferation or increasing apoptosis in two-dimensional cultures in vitro. Integrin-beta4 (ITGB4) expression is significantly reduced, and ITGB4-knockdown mimics the tumor-suppressive effect of netrin-1, implying that ITGB4 is a main target of netrin-1 in constraining PDAC. We further show that netrin-1 signals to UNC5B/FAK to stimulate nitric oxide production, which promotes PP2A-mediated inhibition of the MEK/ERK pathway and decreases phosphorylated-c-Jun recruitment to the ITGB4 promoter. Our findings suggest that netrin-1 can suppress the growth...
language: eng
source:
identifier: E-ISSN: 1949-2553 ; DOI: 10.18632/oncotarget.8348
fulltext: fulltext
issn:
  • 19492553
  • 1949-2553
url: Link


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titleNetrin-1 suppresses the MEK/ERK pathway and ITGB4 in pancreatic cancer.
creatorAn, Xi-Zhou ; Zhao, Zhi-Guo ; Luo, Yu-Xuan ; Zhang, Ran ; Tang, Xiao-Qiang ; Hao, De- Long ; Zhao, Xiang ; Lv, Xiang ; Liu, De- Pei
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ispartofOncotarget, April 26, 2016, Vol.7(17), pp.24719-24733
identifierE-ISSN: 1949-2553 ; DOI: 10.18632/oncotarget.8348
subjectAnimals–Genetics ; Carcinoma, Pancreatic Ductal–Metabolism ; Cell Line, Tumor–Pathology ; Cell Proliferation–Physiology ; Chick Embryo–Genetics ; Extracellular Signal-Regulated MAP Kinases–Metabolism ; Hek293 Cells–Metabolism ; Heterografts–Genetics ; Humans–Metabolism ; Integrin Beta4–Genetics ; MAP Kinase Signaling System–Metabolism ; Mice–Pathology ; Netrin-1–Pathology ; Pancreatic Neoplasms–Pathology ; Integrin Beta4 ; Netrin-1 ; Extracellular Signal-Regulated MAP Kinases ; Mek/Erk ; Pp2a ; Integrin-Beta4 ; Netrin-1 ; Pancreatic Ductal Adenocarcinoma
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descriptionThe axon guidance factor netrin-1 promotes tumorigenesis in multiple types of cancers, particularly at their advanced stages. Here, we investigate whether netrin-1 is involved in the in vivo growth of pancreatic adenocarcinoma. We show that netrin-1 is significantly under-expressed in stage-I/II pancreatic ductal adenocarcinoma (PDAC). Netrin-1 over-expression effectively arrests the growth of xenografted PDAC cells without decreasing cell proliferation or increasing apoptosis in two-dimensional cultures in vitro. Integrin-beta4 (ITGB4) expression is significantly reduced, and ITGB4-knockdown mimics the tumor-suppressive effect of netrin-1, implying that ITGB4 is a main target of netrin-1 in constraining PDAC. We further show that netrin-1 signals to UNC5B/FAK to stimulate nitric oxide production, which promotes PP2A-mediated inhibition of the MEK/ERK pathway and decreases phosphorylated-c-Jun recruitment to the ITGB4 promoter. Our findings suggest that netrin-1 can suppress the growth...
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