Cancer-promoting gene could explain 'paradox'
6 Jan 2015
Researchers at the University of Michigan Comprehensive Cancer Centre have uncovered a cancer-promoting gene linked to both tumour promotion and tumour suppression.
The cellular differentiation and proliferation protein known as TGF-beta has the ability to stop cancer from forming and encourage its growth.
Researchers have now pinpointed Bub1 as the key gene behind this paradox, however.
“When you look at gene expression in cancer, Bub1 is in the top five
Study director Alnawaz Rehemtulla
To promote this paradox, the researchers said that Bub1 is instrumental in regulating TGF-beta receptor, causing the protein to effectively “flip” function.
“Our data that Bub1 is involved at the receptor level is completely unexpected,” said study director Alnawaz Rehemtulla, co-director of the Centre for Molecular Imaging at the University of Michigan Medical School.
“Bub1 is well-known for its role in cell division. But this is the first study that links it to TGF-beta. We think this may explain the paradox of TGF-beta as a tumour promoter and a tumour suppressor,” Rehemtulla said.
The research team screened 720 genes against both lung and breast cancer cells, with Bub1 having emerged as playing a strong role in TGF-beta signalling.
Studies revealed how Bub1 binds to the TGF-beta receptor, allowing it to turn on aggressive cell growth. In contrast, when the researchers blocked Bub1, they found that it shut down the TGF-beta pathway completely.
“When you look at gene expression in cancer, Bub1 is in the top five. In addition, Bub1 expression levels correlate with outcome in patients with lung and breast cancer. But we never knew why. Now that we have that link, we’re a step closer to shutting down this cycle,” Rehemtulla said.
Knowing that Bub1 is expressed in several types of cancer, the Michigan-based research team has developed a compound to target Bub1.
Initial lab testing has suggested that a Bub1 inhibitor could very specifically target Bub1 without causing damage to other parts of the cell - leading to a potential treatment for many types of cancers, the researchers said.
In similar news, there were widespread reports last week that most cancer types could be considered just a case of ’bad luck’.
The reports were taken from a study conducted by scientists at the Johns Hopkins University (JHU), US and published in the journal Science.
“For the media to give the impression that lifestyle isn’t important, based on a misunderstanding of what the research shows, is highly irresponsible
The Stats Guy Blog author Adam
Within the study, the JHU team attempted to understand why some cancers occur more often in some tissue types than in others.
However, the idea that cancer is caused by bad luck as opposed to factors such as smoking has been called ’unfortunate’ and ’distracting’ by Cancer Research UK.
“It just seems a huge shame that something that is, as far as these things go, established scientific fact - that cancer rates are affected by lifestyle - has been called into question,” Henry Scowcroft said, as part of a Cancer Research UK blog post which dissected both the recent media reports and the JHU study.
Likewise, a comment taken from The Stats Guy Blog author Adam, which featured in the Cancer Research UK blog, said: “We often see medical research badly reported in the newspapers. Often it doesn’t matter very much. But here, I think real harm could be done.
“The message that comes across from the media is that cancer is just a matter of luck, so changing your lifestyle won’t make much difference anyway. We know that lifestyle is hugely important not only for cancer, but for many other diseases as well.
“For the media to give the impression that lifestyle isn’t important, based on a misunderstanding of what the research shows, is highly irresponsible.”
