TGFB1/INHBA Homodimer/Nodal-SMAD2/3 Signaling Network: A Pivotal Molecular Target in PDAC Treatment.
Antineoplastic Agents
/ pharmacology
Carcinoma, Pancreatic Ductal
/ drug therapy
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Inhibin-beta Subunits
/ antagonists & inhibitors
Molecular Targeted Therapy
Neoplastic Stem Cells
/ drug effects
Nodal Protein
/ antagonists & inhibitors
Pancreatic Neoplasms
/ drug therapy
Signal Transduction
Smad2 Protein
/ antagonists & inhibitors
Smad3 Protein
/ antagonists & inhibitors
Transforming Growth Factor beta1
/ antagonists & inhibitors
Tumor Microenvironment
INHBA
TGFB1
chemoresistant
nodal
pancreatic cancer
pancreatic cancer stem cells
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
ISSN: 1525-0024
Titre abrégé: Mol Ther
Pays: United States
ID NLM: 100890581
Informations de publication
Date de publication:
03 03 2021
03 03 2021
Historique:
received:
18
06
2020
revised:
17
10
2020
accepted:
02
01
2021
pubmed:
12
1
2021
medline:
19
11
2021
entrez:
11
1
2021
Statut:
ppublish
Résumé
Pancreatic cancer remains a grueling disease that is projected to become the second-deadliest cancer in the next decade. Standard treatment of pancreatic cancer is chemotherapy, which mainly targets the differentiated population of tumor cells; however, it paradoxically sets the roots of tumor relapse by the selective enrichment of intrinsically chemoresistant pancreatic cancer stem cells that are equipped with an indefinite capacity for self-renewal and differentiation, resulting in tumor regeneration and an overall anemic response to chemotherapy. Crosstalk between pancreatic tumor cells and the surrounding stromal microenvironment is also involved in the development of chemoresistance by creating a supportive niche, which enhances the stemness features and tumorigenicity of pancreatic cancer cells. In addition, the desmoplastic nature of the tumor-associated stroma acts as a physical barrier, which limits the intratumoral delivery of chemotherapeutics. In this review, we mainly focus on the transforming growth factor beta 1 (TGFB1)/inhibin subunit beta A (INHBA) homodimer/Nodal-SMAD2/3 signaling network in pancreatic cancer as a pivotal central node that regulates multiple key mechanisms involved in the development of chemoresistance, including enhancement of the stem cell-like properties and tumorigenicity of pancreatic cancer cells, mediating cooperative interactions between pancreatic cancer cells and the surrounding stroma, as well as regulating the deposition of extracellular matrix proteins within the tumor microenvironment.
Identifiants
pubmed: 33429081
pii: S1525-0016(21)00002-2
doi: 10.1016/j.ymthe.2021.01.002
pmc: PMC7934636
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
NODAL protein, human
0
Nodal Protein
0
SMAD2 protein, human
0
SMAD3 protein, human
0
Smad2 Protein
0
Smad3 Protein
0
TGFB1 protein, human
0
Transforming Growth Factor beta1
0
inhibin beta A subunit
0
Inhibin-beta Subunits
93443-12-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
920-936Subventions
Organisme : Cancer Research UK
ID : C59392/A25064
Pays : United Kingdom
Informations de copyright
Copyright © 2021 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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