Yin Yang protein may fuel breast cancer growth

A group of international scientists, led by Imperial College London, have unveiled clues about a mysterious molecule called Yin Yang1 — and revealed that it may fuel tumour growth in breast cancer.

Yin Yang1 is a type of molecule called a transcription factor, which helps activate genes. Although each cell contains around 25,000 genes, only a certain number are switched on at one time, depending on what functions the cell needs to perform.

All cells of the body need Yin Yang1, but scientists were previously unsure whether it helped or hindered cancer growth. To find out if it is friend or foe, the international research team completed in-depth genetic profiling of breast tumours from 47 patients, using a variety of different techniques, including the gene-editing technique CRISPR.

The scientists studied a type of breast cancer called oestrogen-receptor positive, which accounts for 70% of all breast cancers and is treated with hormone therapies. They analysed 34 breast tumours from patients whose cancer had not spread around the body and 13 from another group of patients with more advanced breast tumours, whose cancer had spread.

The team, who included researchers from the European Institute of Oncology, the University of Liverpool and Case Western Reserve University, studied which genes were switched on and off in the tumours. This process, called epigenetics, enables cancer tumours to adapt to their environment and evade treatment — and ultimately survive longer.

To help them track epigenetics the researchers monitored chemical modifications on DNA regions called enhancers — types of ciphers that tell the cell to switch on certain genes when they are activated. The results, published in the journal Nature Medicine, revealed that two particular enhancers, regulating SLC9A3R1 and Yin Yang1 genes, are activated at specific stages when they might help cancer cells grow and evade treatment. In particular, Yin Yang1 was found to switch on SLC9A3R1, which helped tumours grow.

The results thus showed that cancer cells are much more reliant on Yin Yang1 than normal cells, and that this may drive breast cancer growth. They also revealed that tumours change which genes they switch on as they become aggressive, which may affect how they respond to treatment. This suggests doctors should take new tumour samples when a patient’s cancer spreads around the body, according to study author Dr Luca Magnani from Imperial College London.

“At the moment, patients usually have a biopsy when they are first diagnosed with breast cancer,” Dr Magnani said. “Doctors then analyse this tissue sample to identify what type of breast cancer a patient has, as this will dictate the best treatment for them.

“However, our results suggest tumours switch different genes on and off as they progress, and can fundamentally change their ‘appearance’. Therefore, if a tumour becomes more aggressive and spreads around the body, we would advise always taking a second biopsy. The cancer might have changed significantly in this time, and would respond to different treatments. Although taking a second biopsy when a patient’s cancer relapses is becoming much more common, it’s still not happening all the time.”

The team will now study larger numbers of patient samples and follow the same group of patients to track how enhancer activation in these cancers evolves. They will also investigate a type of breast cancer known as triple negative, which is very difficult to treat.

“As expected, our work has raised a lot of questions — and we now need to answer them,” Dr Magnani said. “But it is only through international collaboration — and working as a team — that we can get this vital work done, and hopefully help more patients beat the disease. We could have never done this on our own.”

Image caption: Breast cancer cells (with nucleus shown in green). Image ©Imperial College London.