BACH1 Expression Is Promoted by Tank Binding Kinase 1 (TBK1) in Pancreatic Cancer Cells to Increase Iron and Reduce the Expression of E-Cadherin.
BACH1 Expression Is Promoted by Tank Binding Kinase 1 (TBK1) in Pancreatic Cancer Cells to Increase Iron and Reduce the Expression of E-Cadherin.
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DOI：
10.3390/antiox11081460
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发表时间：
2022-07-27
期刊：
影响因子：
7
通讯作者：
Igarashi, Kazuhiko
中科院分区：
文献类型：
--
作者：
Liu, Liang;Matsumoto, Mitsuyo;Matsui-Watanabe, Miki;Ochiai, Kyoko;Callens, Bert K. K.;Nguyen, Long Chi;Kozuki, Yushi;Tanaka, Miho;Nishizawa, Hironari;Igarashi, Kazuhiko
BTB和CNC同源物1（BACH 1）抑制参与铁、血红素和活性氧代谢的基因的表达，并促进包括胰腺导管腺癌（PDAC）在内的各种癌症的转移。然而，目前尚不清楚BACH 1在PDAC细胞中是如何调节的。Tank结合激酶1（TBK 1）的敲低导致AsPC−1人PDAC细胞中BACH 1 mRNA和蛋白量的减少。基因表达分析的PDAC细胞与敲低TBK 1或BACH 1的建议参与TBK 1和BACH 1的铁稳态的调节。在AsPC−1细胞中，BACH 1敲低后铁蛋白mRNA和蛋白质均增加。流式细胞仪分析显示，BACH 1敲除或敲低的AsPC−1细胞比对照细胞含有更低的不稳定铁，这表明BACH 1通过抑制铁蛋白基因的表达来增加不稳定铁。我们进一步发现，E-钙粘蛋白的表达上调后，螯合细胞内的铁含量。这些结果表明，TBK 1-BACH 1途径通过增加细胞内的不稳定铁来促进癌细胞转移。
BTB and CNC homology 1 (BACH1) represses the expression of genes involved in the metabolism of iron, heme and reactive oxygen species and promotes metastasis of various cancers including pancreatic ductal adenocarcinoma (PDAC). However, it is not clear how BACH1 is regulated in PDAC cells. Knockdown of Tank binding kinase 1 (TBK1) led to reductions of BACH1 mRNA and protein amounts in AsPC−1 human PDAC cells. Gene expression analysis of PDAC cells with knockdown of TBK1 or BACH1 suggested the involvement of TBK1 and BACH1 in the regulation of iron homeostasis. Ferritin mRNA and proteins were both increased upon BACH1 knockdown in AsPC−1 cells. Flow cytometry analysis showed that AsPC−1 cells with BACH1 knockout or knockdown contained lower labile iron than control cells, suggesting that BACH1 increased labile iron by repressing the expression of ferritin genes. We further found that the expression of E-cadherin was upregulated upon the chelation of intracellular iron content. These results suggest that the TBK1-BACH1 pathway promotes cancer cell metastasis by increasing labile iron within cells.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
8
作者：
Cruz, Victoria H.;Amer, Emily N.;Brekken, Rolf A.
通讯作者：
Brekken, Rolf A.
影响因子：
8.8
作者：
Goodwin JM;Dowdle WE;DeJesus R;Wang Z;Bergman P;Kobylarz M;Lindeman A;Xavier RJ;McAllister G;Nyfeler B;Hoffman G;Murphy LO
通讯作者：
Murphy LO
DOI：
10.1016/j.bbagrm.2012.06.001
发表时间：
2012-11
影响因子：
4.7
作者：
Hou, Weihong;Tian, Qing;Steuerwald, Nury M.;Schrum, Laura W.;Bonkovsky, Herbert L.
通讯作者：
Bonkovsky, Herbert L.
影响因子：
64.5
作者：
Chien, Yuchen;Kim, Sungchan;White, Michael A.
通讯作者：
White, Michael A.