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SMAD4 and the TGFβ Pathway in Patients with Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death worldwide. PDAC is an aggressive disease with an 11-month median overall survival and a five-year survival of less than 5%. Incidence of PDAC is constantly increasing and is predicted to become the second leading cau...

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Autores principales: Dardare, Julie, Witz, Andréa, Merlin, Jean-Louis, Gilson, Pauline, Harlé, Alexandre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278913/
https://www.ncbi.nlm.nih.gov/pubmed/32429474
http://dx.doi.org/10.3390/ijms21103534
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author Dardare, Julie
Witz, Andréa
Merlin, Jean-Louis
Gilson, Pauline
Harlé, Alexandre
author_facet Dardare, Julie
Witz, Andréa
Merlin, Jean-Louis
Gilson, Pauline
Harlé, Alexandre
author_sort Dardare, Julie
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death worldwide. PDAC is an aggressive disease with an 11-month median overall survival and a five-year survival of less than 5%. Incidence of PDAC is constantly increasing and is predicted to become the second leading cause of cancer in Western countries within a decade. Despite research and therapeutic development, current knowledge about PDAC molecular mechanisms still needs improvements and it seems crucial to identify novel therapeutic targets. Genomic analyses of PDAC revealed that transforming growth factor β (TGFβ) signaling pathways are modified and the SMAD4 gene is altered in 47% and 60% of cases, respectively, highlighting their major roles in PDAC development. TGFβ can play a dual role in malignancy depending on the context, sometimes as an inhibitor and sometimes as an inducer of tumor progression. TGFβ signaling was identified as a potent inducer of epithelial-to-mesenchymal transition (EMT), a process that confers migratory and invasive properties to epithelial cells during cancer. Therefore, aberrant TGFβ signaling and EMT are linked to promoting PDAC aggressiveness. TGFβ and SMAD pathways were extensively studied but the mechanisms leading to cancer promotion and development still remain unclear. This review aims to describe the complex role of SMAD4 in the TGFβ pathway in patients with PDAC.
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spelling pubmed-72789132020-06-15 SMAD4 and the TGFβ Pathway in Patients with Pancreatic Ductal Adenocarcinoma Dardare, Julie Witz, Andréa Merlin, Jean-Louis Gilson, Pauline Harlé, Alexandre Int J Mol Sci Review Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death worldwide. PDAC is an aggressive disease with an 11-month median overall survival and a five-year survival of less than 5%. Incidence of PDAC is constantly increasing and is predicted to become the second leading cause of cancer in Western countries within a decade. Despite research and therapeutic development, current knowledge about PDAC molecular mechanisms still needs improvements and it seems crucial to identify novel therapeutic targets. Genomic analyses of PDAC revealed that transforming growth factor β (TGFβ) signaling pathways are modified and the SMAD4 gene is altered in 47% and 60% of cases, respectively, highlighting their major roles in PDAC development. TGFβ can play a dual role in malignancy depending on the context, sometimes as an inhibitor and sometimes as an inducer of tumor progression. TGFβ signaling was identified as a potent inducer of epithelial-to-mesenchymal transition (EMT), a process that confers migratory and invasive properties to epithelial cells during cancer. Therefore, aberrant TGFβ signaling and EMT are linked to promoting PDAC aggressiveness. TGFβ and SMAD pathways were extensively studied but the mechanisms leading to cancer promotion and development still remain unclear. This review aims to describe the complex role of SMAD4 in the TGFβ pathway in patients with PDAC. MDPI 2020-05-16 /pmc/articles/PMC7278913/ /pubmed/32429474 http://dx.doi.org/10.3390/ijms21103534 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 Review
Dardare, Julie
Witz, Andréa
Merlin, Jean-Louis
Gilson, Pauline
Harlé, Alexandre
SMAD4 and the TGFβ Pathway in Patients with Pancreatic Ductal Adenocarcinoma
title SMAD4 and the TGFβ Pathway in Patients with Pancreatic Ductal Adenocarcinoma
title_full SMAD4 and the TGFβ Pathway in Patients with Pancreatic Ductal Adenocarcinoma
title_fullStr SMAD4 and the TGFβ Pathway in Patients with Pancreatic Ductal Adenocarcinoma
title_full_unstemmed SMAD4 and the TGFβ Pathway in Patients with Pancreatic Ductal Adenocarcinoma
title_short SMAD4 and the TGFβ Pathway in Patients with Pancreatic Ductal Adenocarcinoma
title_sort smad4 and the tgfβ pathway in patients with pancreatic ductal adenocarcinoma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278913/
https://www.ncbi.nlm.nih.gov/pubmed/32429474
http://dx.doi.org/10.3390/ijms21103534
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