A molecular “switch” that makes cells in breast cancer tumors become aggressive has been discovered by scientists.

Compared to normal cells, cancer cells experience higher oxidative stress, which is the imbalance between the production of free radicals and the body’s antioxidant defenses. The antioxidant protein called manganese superoxide dismutase (MnSOD) is essential for cancer cells to cope with their high oxidative stress.

Too much MnSOD can cause a localized tumor to become aggressive and spread to neighboring organs, the new research shows.

This is especially true for triple negative breast cancer, a subtype of estrogen-independent breast cancer, which affects about 13 percent of all female breast cancer patients worldwide.

Increased MnSOD Expression

Loo Ser Yue, first author of the study and a former graduate student at the National University of Singapore (NUS), explains:

“MnSOD expression is decreased during the initial stages of cancer development. However, as the cancer advances, MnSOD expression increases and such high MnSOD levels are typically observed in triple negative breast cancer patients. In fact, we have shown that less aggressive tumors, when artificially made to increase MnSOD protein levels, adopt an aggressive behavior.

Our study shows that the amount of MnSOD levels in the tumor cell determines the predominant reactive oxygen species that will tell the tumor cells whether to stay put or to transform into an invasive form that is capable of moving to distal parts of the body.”

Due to the lack of well-defined molecular targets in triple negative breast cancer patients, current treatment options rely heavily on chemotherapy, which is highly non-specific and has adverse side effects.

Suppressing MnSOD expression or activity may make the tumors less aggressive and more sensitive to chemotherapy and conventional anticancer drugs, thereby improving treatment outcomes, says Alan Prem Kumar, a research assistant professor at NUS Yong Loo Lin School of Medicine.

The team hopes to design small molecules targeting MnSOD to selectively kill cancer cells.

Loo Ser Yue, Hirpara Jayshree L., Pandey Vijay, Tan Tuan Zea, Yap Celestial T., Lobie Peter E., Thiery Jean Paul, Goh Boon Cher, Pervaiz Shazib, Clément Marie-Véronique, and Kumar Alan Prem Manganese Superoxide Dismutase Expression Regulates the Switch Between an Epithelial and a Mesenchymal-Like Phenotype in Breast Carcinoma Antioxidants & Redox Signaling. August 2016, 25(6): 283-299. doi:10.1089/ars.2015.6524

Image: National University of Singapore

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