Fatty acid binding protein 4 regulates pancreatic cancer cell proliferation via activation of nuclear factor E2-related factor 2.
Cell proliferation
FABP4
Fatty acid binding protein 4
NRF2
Pancreatic cancer
Journal
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery
ISSN: 1878-7533
Titre abrégé: Surg Obes Relat Dis
Pays: United States
ID NLM: 101233161
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
received:
04
03
2021
revised:
18
11
2021
accepted:
01
12
2021
pubmed:
10
1
2022
medline:
5
4
2022
entrez:
9
1
2022
Statut:
ppublish
Résumé
Obesity and diabetes are associated with an increased incidence of pancreatic cancer. Fatty acid binding protein 4 (FABP4), noted to be higher in patients with severe obesity, is linked to the development and progression of several cancers, and its level in the circulation decreases after bariatric surgery. In this paper, we evaluate the role of FABP4 in pancreatic cancer progression. University Hospital and Laboratories, United States. When Panc-1 (human) and Pan02 (mouse) pancreatic cancer cells were treated with FABP4 or the-single-point mutant FABP4 (R126Q, fatty acid binding site mutant), only FABP4 stimulated cellular proliferation. The transcriptional activity of nuclear factor E2-related factor 2 (NRF2) was increased in response to FABP4 but not the R126Q. FABP4 treatment also led to downregulation of reactive oxygen species (ROS) activity. Consistent with induced cell propagation by FABP4, the growth of Pan02 tumor was decreased in FABP4-null animals compared with C57BL/6J controls. These results suggest that FABP4 increases pancreatic cancer proliferation via activation of NRF2 and downregulation of ROS activity.
Sections du résumé
BACKGROUND
Obesity and diabetes are associated with an increased incidence of pancreatic cancer. Fatty acid binding protein 4 (FABP4), noted to be higher in patients with severe obesity, is linked to the development and progression of several cancers, and its level in the circulation decreases after bariatric surgery.
OBJECTIVE
In this paper, we evaluate the role of FABP4 in pancreatic cancer progression.
SETTING
University Hospital and Laboratories, United States.
METHODS AND RESULTS
When Panc-1 (human) and Pan02 (mouse) pancreatic cancer cells were treated with FABP4 or the-single-point mutant FABP4 (R126Q, fatty acid binding site mutant), only FABP4 stimulated cellular proliferation. The transcriptional activity of nuclear factor E2-related factor 2 (NRF2) was increased in response to FABP4 but not the R126Q. FABP4 treatment also led to downregulation of reactive oxygen species (ROS) activity. Consistent with induced cell propagation by FABP4, the growth of Pan02 tumor was decreased in FABP4-null animals compared with C57BL/6J controls.
CONCLUSION
These results suggest that FABP4 increases pancreatic cancer proliferation via activation of NRF2 and downregulation of ROS activity.
Identifiants
pubmed: 34998697
pii: S1550-7289(21)00571-2
doi: 10.1016/j.soard.2021.12.002
pmc: PMC8960336
mid: NIHMS1763188
pii:
doi:
Substances chimiques
FABP4 protein, human
0
Fatty Acid-Binding Proteins
0
NF-E2-Related Factor 2
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
485-493Subventions
Organisme : NIDDK NIH HHS
ID : T32 DK108733
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK053189
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK128325
Pays : United States
Organisme : NIDDK NIH HHS
ID : R56 DK053189
Pays : United States
Organisme : NIDDK NIH HHS
ID : R21 DK122832
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.
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