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The novel truncated isoform of human manganese superoxide dismutase has a differential role in promoting metastasis of lung cancer cells
Author(s) -
Li Shuaiguang,
Yang Enze,
Shen Lianghua,
Niu Dewei,
Breitzig Mason,
Tan Lee Charles,
Wu Xiaocong,
Huang Meiyan,
Sun Hanxiao,
Wang Feng
Publication year - 2018
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10972
Subject(s) - gene isoform , metastasis , vimentin , protein kinase b , gene knockdown , biology , cancer research , cancer cell , alternative splicing , a549 cell , superoxide dismutase , microbiology and biotechnology , cancer , apoptosis , signal transduction , oxidative stress , gene , immunology , endocrinology , immunohistochemistry , biochemistry , genetics
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.