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:
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery
影响因子:
--
通讯作者:
Yamamoto M
Yamamoto M
中科院分区:
其他
文献类型:
--
作者:
Wirth K;Shinoda S;Sato-Dahlman M;Dickey DM;Bernlohr DA;Ikramuddin S;Yamamoto M

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肥胖和糖尿病与胰腺癌发病率增加有关。脂肪酸结合蛋白4(FABP4)在重度肥胖患者中含量较高,与多种癌症的发生和发展有关,且在减肥手术后其在血液中的水平会降低。在本文中,我们评估了FABP4在胰腺癌进展中的作用。 当用人胰腺癌细胞Panc - 1和小鼠胰腺癌细胞Pan02分别用FABP4或R126Q FABP4(脂肪酸结合位点突变体)处理时,只有FABP4刺激细胞增殖。核因子E2相关因子2(NRF2)的转录活性因FABP4而增加,但R126Q不会。FABP4处理还导致活性氧(ROS)活性下调。与FABP4诱导的细胞增殖一致,与C57BL/6J对照组相比,FABP4缺失动物中Pan02肿瘤的生长减缓。 这些结果表明,FABP4通过激活Nrf2和下调ROS活性来促进胰腺癌增殖。
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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