Discovery of protein’s role in prostate cancer could lead to new treatments

It's a disease affecting those closest to us – our fathers, brothers and sons.

Prostate cancer impacts one in six men in Canada. Last year, roughly 24,600 men
were diagnosed with the disease.

Most types of prostate cancer are curable if caught and treated early. But little is
understood about the mechanisms that cause a tumour to metastasize and spread to
other parts of the body.

Damu Tang, an associate professor of medicine in the Division of Nephrology of
McMaster University's Michael G. DeGroote School of Medicine and St. Joseph's
Healthcare Hamilton, has spent nearly a decade – and searched more than a million
genes – to better understand the molecular underpinnings of prostate cancer
progression.

His research, published today in Nature Communications, shows for the first time
the role of a specific protein – MAN2C1 – in prostate cancer development. The finding is
significant because prostate cancer patients with increased levels of MAN2C1 appear to
face more aggressive forms of the disease.

“This research could serve a diagnostic purpose in terms of likelihood of whether
prostate cancers at early stages will progress into metastatic tumours,” said Tang, who
has a joint appointment in the Division of Urology, Department of Surgery at McMaster.
“Patients with high levels of MAN2C1 may need more aggressive therapies when their
cancers are still at early stages in order to prevent the development of metastatic
cancer.”

It's been known for some time that another protein, PTEN, is a powerful tumour
suppressor. Clinical observations have shown that half of advanced prostate cancers
either have no PTEN or reduced PTEN function.

Tang and his research team set out to understand how PTEN function becomes
impaired in advanced prostate cancers. In the process, they discovered MAN2C1 and the
role it plays in reducing PTEN function.

The research group found increases in the MAN2C1 protein in PTEN-positive
prostate cancer cells dramatically increased the likelihood of cancers forming in mice.
Additional research showed that in 659 prostate cancer patients, approximately 60 per
cent of their prostate tumors had normal PTEN. Among these tumors, 80 per cent had
increased MAN2C1.

The researchers concluded that increases in MAN2C1 in PTEN-positive prostate
cancers enhance prostate cancer recurrence, meaning that patients with high levels of
MAN2C1 have an increased risk of their tumors developing into metastatic cancer.

The next step for the researchers will be to look for ways to block the ability of
MAN2C1 to impair PTEN function, Tang said. That could lead to the development of new
therapies for patients with prostate cancer.

Tang's research was funded by Prostate Cancer Canada, the Canada Foundation for
Innovation, St. Joseph's Healthcare Hamilton and Canadian Institutes of Health Research.