The novel truncated isoform of human manganese superoxide dismutase has a differential role in promoting metastasis of lung cancer cells
| Autor: | Hanxiao Sun, Mason Breitzig, Dewei Niu, Meiyan Huang, Enze Yang, Shuaiguang Li, Lianghua Shen, Feng Wang, Lee Charles Tan, Xiaocong Wu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
A549 cell Gene isoform Gene knockdown biology Chemistry Cell Vimentin Cell Biology General Medicine medicine.disease Metastasis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure 030220 oncology & carcinogenesis biology.protein medicine Cancer research Signal transduction Protein kinase B |
| Zdroj: | Cell Biology International. 42:1030-1040 |
| ISSN: | 1065-6995 |
| Popis: | Growing evidences have demonstrated alternative splicing makes great contribution to tumor metastasis since multiple protein isoforms from a single gene that often display different functions in the cell. Human manganese superoxide dismutase (hMnSOD) was revealed dysregulation in progress of tumor metastasis, while the effect of hMnSOD isoforms on metastasis remained unclear. In this study, we showed a novel truncated hMnSOD isoform hMnSOD183, which lacked 39 amino acids compared with hMnSOD222. We expressed two hMnSOD protein isoforms in Escherichia coli, respectively, and found that the MnSOD activity of truncated hMnSOD isoform was especially weaker. In 95-D cells, mRNA levels of hMnSOD variants and MnSOD activity were significantly increased than that in A549 cells. Furthermore, the hMnSODc exhibited lower mRNA level than hMnSODa/b in A549 and 95-D cells. Additionally, the effects of two isoforms were assessed about cell invasion, overexpression of hMnSOD222 but not hMnSOD183 promoted 95-D cells metastasis, and hMnSOD knockdown significantly reduced cells invasive behavior. Overexpression of hMnSOD isoforms also caused changes of metastasis associated proteins, such as up-regulation of MMPs, VEGF and Vimentin and down-regulation of E-cadherin. Moreover, overexpression of hMnSOD183 had weaker effect on metastasis related signaling proteins, such as Akt, JNK and IKKβ, compared to hMnSOD222. In conclusion, our study identified that hMnSOD isoforms induced lung cancer cells invasion through Akt-JNK-IKKβ signaling pathways and the hMnSOD183 isoform played a weaker role than hMnSOD222. Characterization of hMnSOD isoforms is useful for future investigation on metastasis of lung cancer cells. |
| Databáze: | OpenAIRE |
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