<i>BACH1</i> Expression Is Promoted by Tank Binding Kinase 1 (<i>TBK1</i>) in Pancreatic Cancer Cells to Increase Iron and Reduce the Expression of E-Cadherin
BTB and CNC homology 1 (<i>BACH1</i>) 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 <i>BACH1</i>...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/11/8/1460 |
| Summary: | BTB and CNC homology 1 (<i>BACH1</i>) 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 <i>BACH1</i> is regulated in PDAC cells. Knockdown of Tank binding kinase 1 (<i>TBK1</i>) led to reductions of <i>BACH1</i> mRNA and protein amounts in AsPC−1 human PDAC cells. Gene expression analysis of PDAC cells with knockdown of <i>TBK1</i> or <i>BACH1</i> suggested the involvement of <i>TBK1</i> and <i>BACH1</i> in the regulation of iron homeostasis. Ferritin mRNA and proteins were both increased upon <i>BACH1</i> knockdown in AsPC−1 cells. Flow cytometry analysis showed that AsPC−1 cells with <i>BACH1</i> knockout or knockdown contained lower labile iron than control cells, suggesting that <i>BACH1</i> 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 <i>TBK1</i>-<i>BACH1</i> pathway promotes cancer cell metastasis by increasing labile iron within cells. |
|---|---|
| ISSN: | 2076-3921 |