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RAGE Up-Regulation Differently Affects Cell Proliferation and Migration in Pancreatic Cancer Cells

The receptor for advanced glycation end products (RAGE) contributes to many cellular aspects of pancreatic cancer including cell proliferation, migration, and survival. Studies have shown that RAGE activation by its ligands promotes pancreatic tumor growth by stimulating both cell proliferation and...

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Autores principales: Swami, Priyanka, Thiyagarajan, Swetha, Vidger, Arianna, Indurthi, Venkata S. K., Vetter, Stefan W., Leclerc, Estelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589276/
https://www.ncbi.nlm.nih.gov/pubmed/33086527
http://dx.doi.org/10.3390/ijms21207723
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author Swami, Priyanka
Thiyagarajan, Swetha
Vidger, Arianna
Indurthi, Venkata S. K.
Vetter, Stefan W.
Leclerc, Estelle
author_facet Swami, Priyanka
Thiyagarajan, Swetha
Vidger, Arianna
Indurthi, Venkata S. K.
Vetter, Stefan W.
Leclerc, Estelle
author_sort Swami, Priyanka
collection PubMed
description The receptor for advanced glycation end products (RAGE) contributes to many cellular aspects of pancreatic cancer including cell proliferation, migration, and survival. Studies have shown that RAGE activation by its ligands promotes pancreatic tumor growth by stimulating both cell proliferation and migration. In this study, we investigated the effect of RAGE up-regulation on the proliferation and migration of the human pancreatic cancer Panc-1 cell-line. We show that moderate overexpression of RAGE in Panc-1 cells results in increased cell proliferation, but decreased cell migration. The observed cellular changes were confirmed to be RAGE-specific and reversible by using RAGE-specific siRNAs and the small molecule RAGE inhibitor FPS-ZM1. At the molecular level, we show that RAGE up-regulation was associated with decreased activity of FAK, Akt, Erk1/2, and NF-κB signaling pathways and greatly reduced levels of α2 and β1 integrin expression, which is in agreement with the observed decreases in cell migration. We also demonstrate that RAGE up-regulation changes the expression of key molecular markers of epithelial-to-mesenchymal transition (EMT). Our results suggest that in the absence of stimulation by external ligands, RAGE up-regulation can differently modulate cell proliferation and migration in pancreatic cancer cells and regulates partly EMT.
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spelling pubmed-75892762020-10-29 RAGE Up-Regulation Differently Affects Cell Proliferation and Migration in Pancreatic Cancer Cells Swami, Priyanka Thiyagarajan, Swetha Vidger, Arianna Indurthi, Venkata S. K. Vetter, Stefan W. Leclerc, Estelle Int J Mol Sci Article The receptor for advanced glycation end products (RAGE) contributes to many cellular aspects of pancreatic cancer including cell proliferation, migration, and survival. Studies have shown that RAGE activation by its ligands promotes pancreatic tumor growth by stimulating both cell proliferation and migration. In this study, we investigated the effect of RAGE up-regulation on the proliferation and migration of the human pancreatic cancer Panc-1 cell-line. We show that moderate overexpression of RAGE in Panc-1 cells results in increased cell proliferation, but decreased cell migration. The observed cellular changes were confirmed to be RAGE-specific and reversible by using RAGE-specific siRNAs and the small molecule RAGE inhibitor FPS-ZM1. At the molecular level, we show that RAGE up-regulation was associated with decreased activity of FAK, Akt, Erk1/2, and NF-κB signaling pathways and greatly reduced levels of α2 and β1 integrin expression, which is in agreement with the observed decreases in cell migration. We also demonstrate that RAGE up-regulation changes the expression of key molecular markers of epithelial-to-mesenchymal transition (EMT). Our results suggest that in the absence of stimulation by external ligands, RAGE up-regulation can differently modulate cell proliferation and migration in pancreatic cancer cells and regulates partly EMT. MDPI 2020-10-19 /pmc/articles/PMC7589276/ /pubmed/33086527 http://dx.doi.org/10.3390/ijms21207723 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Swami, Priyanka
Thiyagarajan, Swetha
Vidger, Arianna
Indurthi, Venkata S. K.
Vetter, Stefan W.
Leclerc, Estelle
RAGE Up-Regulation Differently Affects Cell Proliferation and Migration in Pancreatic Cancer Cells
title RAGE Up-Regulation Differently Affects Cell Proliferation and Migration in Pancreatic Cancer Cells
title_full RAGE Up-Regulation Differently Affects Cell Proliferation and Migration in Pancreatic Cancer Cells
title_fullStr RAGE Up-Regulation Differently Affects Cell Proliferation and Migration in Pancreatic Cancer Cells
title_full_unstemmed RAGE Up-Regulation Differently Affects Cell Proliferation and Migration in Pancreatic Cancer Cells
title_short RAGE Up-Regulation Differently Affects Cell Proliferation and Migration in Pancreatic Cancer Cells
title_sort rage up-regulation differently affects cell proliferation and migration in pancreatic cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589276/
https://www.ncbi.nlm.nih.gov/pubmed/33086527
http://dx.doi.org/10.3390/ijms21207723
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