What is it about?

We found that acetylation transforms SOD2, a tumor suppressor, into a cancer promoting enzyme.

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Why is it important?

1) SOD2 has been known to have a dichotomous role as a tumor suppressor in healthy cells and a pro-cancer enzyme in established tumors. Our study shows that acetylation, a modification associated with metabolic dysfunction, promotes structural changes to the enzyme directly associated with this change in function. 2) The structural uniqueness of FeSOD2 as well as its localization to the nucleus may enable the development of better, targeted therapies for breast cancer.

Perspectives

It has been known for many years that SOD2 has a dichotomous role functioning as a tumor suppressor in healthy cells but as a tumor-promoting enzyme in established tumors. We demonstrated a novel function that is unleashed by acetylation that drives this functional transformation. In addition, we show that FeSOD2 is a unique demethylase that requires H2O2 as substrate instead of oxygen and a-ketoglurate. While H2O2 is normally more abundant in tumor cells than in health cells, a-ketoglutarate and oxygen are scarce. Hence we provide a novel mechanism for tumor cell reprogramming that can occur in hypoxic microenvironments.

Marcelo Bonini
Northwestern University

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This page is a summary of: Nuclear-localized, iron-bound superoxide dismutase-2 antagonizes epithelial lineage programs to promote stemness of breast cancer cells via a histone demethylase activity, Proceedings of the National Academy of Sciences, July 2022, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2110348119.
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