2018
DOI: 10.1002/cbin.10972
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The novel truncated isoform of human manganese superoxide dismutase has a differential role in promoting metastasis of lung cancer cells

Abstract: 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 t… Show more

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Cited by 5 publications
(3 citation statements)
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“…These results are consistent with the idea that a more malignant phenotype is associated with upregulation of SOD2. Indeed, SOD2 levels are reported to increase during metastatic progression and in highly aggressive tumor cell lines 33‐36 . Prior studies have also shown that elevated antioxidant enzyme expression is a necessary survival adaptation during tumor progression 37 .…”
Section: Discussionmentioning
confidence: 99%
“…These results are consistent with the idea that a more malignant phenotype is associated with upregulation of SOD2. Indeed, SOD2 levels are reported to increase during metastatic progression and in highly aggressive tumor cell lines 33‐36 . Prior studies have also shown that elevated antioxidant enzyme expression is a necessary survival adaptation during tumor progression 37 .…”
Section: Discussionmentioning
confidence: 99%
“…The upregulation of MnSOD is involved in the development of cancer [ 19 ]. It has been shown that MnSOD overexpression promotes metastasis and resistance in lung cancer [ 20 , 21 ]. Our previous study showed that it could contribute to stemness of LCSLCs by the upregulation of FoxM1 [ 10 ].…”
Section: Discussionmentioning
confidence: 99%
“…The SOD2 reference structure ( Figure 7E ), is quite different from the SOD2 isoform 2 structure ( Figure 7F ), where an ES event causes a helix loss in the isoform. Interestingly, a critical residue 98H manganese ion (Mn 2+ ) binding site is lost in SOD2 isoform, and it is believed to decrease the activity of isoform 2 51 . We also observe that in the reference structure, the four Mn 2+ binding sites (50H, 98H, 183D and 187H) are clustered together, while in the isoform structure, the remaining binding sites do not form a binding cluster with 50H located away from the 144D and 148H, which could also explain the decrease of superoxide dismutase activity.…”
Section: Resultsmentioning
confidence: 99%