Switching off breast cancer aggression

9 November 2016 | Research
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Cells showing the presence of Vimentin (in red), a protein often used as a marker of aggressive cells or cells converting to a form capable of invading other organs

A team of NUS scientists has discovered a molecular “switch” that makes cancer cells in breast cancer tumours more aggressive. The findings were published in the journal Antioxidants & Redox Signaling in August 2016.

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 defences. The major antioxidant protein Manganese Superoxide Dismutase (MnSOD) is essential for cancer cells to cope with their high oxidative stress.

However, the team — Dr Alan Prem Kumar, a Research Assistant Professor at NUS Yong Loo Lin School of Medicine (NUS Medicine) and the Cancer Science Institute of Singapore at NUS; together with Professor Shazib Pervaiz and Associate Professor Marie-Veronique Clement from NUS Medicine — found that too much MnSOD activates a molecular programme that causes a localised tumour to become aggressive and spread to neighbouring organs. This is especially true for triple negative breast cancer, a subtype of estrogen-independent breast cancer, which affects about 13 per cent of all female breast cancer patients worldwide.

“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 tumours, when artificially made to increase MnSOD protein levels, adopt an aggressive behaviour. Our study shows that the amount of MnSOD levels in the tumour cell determines the predominant reactive oxygen species that will tell the tumour cells whether to stay put or to transform into an invasive form that is capable of moving to distal parts of the body,” explained Dr Loo Ser Yue, first author of the study.

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 can make the tumours less aggressive and more sensitive to chemotherapy and conventional anticancer drugs, thereby improving treatment outcomes, said Dr Kumar. The novel strategy would also resensitise patients who had developed resistance to such conventional drugs and could possibly be used in the treatment of aggressive cancers beyond breast cancer.

Moving forward, the team hopes to design small molecules targeting MnSOD to selectively kill cancer cells. 

See press release.