Fatty acid binding protein 4 regulates pancreatic cancer cell proliferation via activation of nuclear factor E2-related factor 2.
Fatty acid binding protein 4 regulates pancreatic cancer cell proliferation via activation of nuclear factor E2-related factor 2.
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DOI:
10.1016/j.soard.2021.12.002
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发表时间:
2022-04
期刊:
影响因子:
--
通讯作者:
Yamamoto M
中科院分区:
文献类型:
--
作者:
Wirth K;Shinoda S;Sato-Dahlman M;Dickey DM;Bernlohr DA;Ikramuddin S;Yamamoto M
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 circulation decreases after bariatric surgery. In this paper, we evaluated the role of FABP4 in pancreatic cancer progression. When Panc-1 (human) and Pan02 (Mouse) pancreatic cancer cells were treated with FABP4 or R126Q FABP4 (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 leaded to downregulation of reactive oxygen species (ROS) activity. Consistent with induced cell propagation by FABP4, the tumor growth of Pan02 tumor was decreased in FABP4 null animals compared to C57BL/6J controls. These results suggest that FABP4 increases pancreatic cancer proliferation via activation of Nrf2 and downregulation of ROS activity.
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