| RRC ID |
74908
|
| 著者 |
Arai W, Konno T, Kohno T, Kodera Y, Tsujiwaki M, Shindo Y, Chiba H, Miyajima M, Sakuma Y, Watanabe A, Kojima T.
|
| タイトル |
Downregulation of angulin-1/LSR induces malignancy via upregulation of EGF-dependent claudin-2 and TGF-β-dependent cell metabolism in human lung adenocarcinoma A549 cells.
|
| ジャーナル |
Oncotarget
|
| Abstract |
Abnormal expression of bicellular tight junction claudins, including claudin-2 are observed during carcinogenesis in human lung adenocarcinoma. However, little is known about the role of tricellular tight junction molecule angulin-1/lipolysis-stimulated lipoprotein receptor (LSR). In the lung adenocarcinoma tissues examined in the present study, expression of claudin-2 was higher than in normal lung tissues, while angulin-1/LSR was poorly or faintly expressed. We investigated how loss of angulin-1/LSR affects the malignancy of lung adenocarcinoma cell line A549 and normal human lung epithelial (HLE) cells. The EGF receptor tyrosine kinase inhibitor AG1478 prevented the increase of claudin-2 expression induced by EGF in A549 cells. Knockdown of LSR induced expression of claudin-2 at the protein and mRNA levels and AG1478 prevented the upregulation of claudin-2 in A549 cells. Knockdown of LSR induced cell proliferation, cell migration and cell metabolism in A549 cells. Knockdown of claudin-2 inhibited the cell proliferation but did not affect the cell migration or cell metabolism of A549 cells. The TGF-β type I receptor inhibitor EW-7197 prevented the decrease of LSR and claudin-2 induced by TGF-β1 in A549 cells and 2D culture of normal HLE cells. EW-7197 prevented the increase of cell migration and cell metabolism induced by TGF-β1 in A549 cells. EW-7197 prevented the increase of epithelial permeability of FITC-4kD dextran induced by TGF-β1 in 2.5D culture of normal HLE cells. In conclusion, downregulation of angulin-1/LSR induces malignancy via EGF-dependent claudin-2 and TGF-β-dependent cell metabolism in human lung adenocarcinoma.
|
| 巻・号 |
14
|
| ページ |
261-275
|
| 公開日 |
2023-3-24
|
| DOI |
10.18632/oncotarget.27728
|
| PII |
27728
|
| PMID |
36961882
|
| PMC |
PMC10038356
|
| MeSH |
A549 Cells
Adenocarcinoma of Lung* / genetics
Adenocarcinoma of Lung* / metabolism
Claudin-2 / metabolism
Down-Regulation
Epidermal Growth Factor / metabolism
Humans
Lung Neoplasms* / genetics
Lung Neoplasms* / metabolism
Tight Junctions / metabolism
Transforming Growth Factor beta / metabolism
Transforming Growth Factor beta1 / metabolism
Up-Regulation
|
| IF |
5.168
|
| リソース情報 |
| ヒト・動物細胞 |
A549 |
