RAGE Up-Regulation Differently Affects Cell Proliferation and Migration in Pancreatic Cancer Cells.
RAGE Up-Regulation Differently Affects Cell Proliferation and Migration in Pancreatic Cancer Cells.
复制标题
愤怒上调对胰腺癌细胞的细胞增殖和迁移的影响不同。
DOI：
10.3390/ijms21207723
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发表时间：
2020-10-19
影响因子：
5.6
通讯作者：
Leclerc E
中科院分区：
文献类型：
--
作者：
Swami P;Thiyagarajan S;Vidger A;Indurthi VSK;Vetter SW;Leclerc E
晚期糖基化终末产物受体（receptor for advanced glycation end products，简称AGEs）参与了胰腺癌的许多细胞方面，包括细胞增殖、迁移和存活。研究表明，由其配体激活的TNF-α通过刺激细胞增殖和迁移促进胰腺肿瘤生长。在这项研究中，我们研究了上调对人胰腺癌Panc-1细胞系的增殖和迁移的影响。我们发现，在Panc-1细胞中适度过表达的p53导致细胞增殖增加，但细胞迁移减少。通过使用RAGE特异性siRNA和小分子抑制剂FPS-ZM 1证实观察到的细胞变化是RAGE特异性的和可逆的。在分子水平上，我们发现，TNF-α上调与FAK、Akt、Erk 1/2和NF-κB信号通路的活性降低以及α2和β1整合素表达水平的显著降低相关，这与观察到的细胞迁移减少一致。我们还证明，上调表达改变了上皮间质转化（EMT）的关键分子标志物的表达。我们的研究结果表明，在缺乏外部配体的刺激下，上调可以不同地调节胰腺癌细胞的细胞增殖和迁移，并部分调节EMT。
The receptor for advanced glycation end products (RAGE) contributes to many cellular aspects of pancreatic cancer including cell proliferation, migration, and survival. Studies have shown that RAGE activation by its ligands promotes pancreatic tumor growth by stimulating both cell proliferation and migration. In this study, we investigated the effect of RAGE up-regulation on the proliferation and migration of the human pancreatic cancer Panc-1 cell-line. We show that moderate overexpression of RAGE in Panc-1 cells results in increased cell proliferation, but decreased cell migration. The observed cellular changes were confirmed to be RAGE-specific and reversible by using RAGE-specific siRNAs and the small molecule RAGE inhibitor FPS-ZM1. At the molecular level, we show that RAGE up-regulation was associated with decreased activity of FAK, Akt, Erk1/2, and NF-κB signaling pathways and greatly reduced levels of α2 and β1 integrin expression, which is in agreement with the observed decreases in cell migration. We also demonstrate that RAGE up-regulation changes the expression of key molecular markers of epithelial-to-mesenchymal transition (EMT). Our results suggest that in the absence of stimulation by external ligands, RAGE up-regulation can differently modulate cell proliferation and migration in pancreatic cancer cells and regulates partly EMT.
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影响因子：
11.2
作者：
Dillon RL;Marcotte R;Hennessy BT;Woodgett JR;Mills GB;Muller WJ
通讯作者：
Muller WJ
影响因子：
15.9
作者：
Caveda, L;MartinPadura, L;Dejana, E
通讯作者：
Dejana, E
影响因子：
3.5
作者：
Bhawal, UK;Ozaki, Y;Kato, Y
通讯作者：
Kato, Y
影响因子：
4.7
作者：
Bartling, B;Hofmann, HS;Simm, A
通讯作者：
Simm, A
DOI：
10.1158/1078-0432.ccr-12-0221
发表时间：
2012-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Arumugam T;Ramachandran V;Gomez SB;Schmidt AM;Logsdon CD
通讯作者：
Logsdon CD