Using cuting edge techniques, Swiss researchers find a new cancer-fighting protein.
Each year, around 31,000 people in the United States develop liver cancer, also known as hepatocellular carcinoma .
And, roughly 24,000 people will die from the disease.
Worryingly, over the past few decades, rates of liver cancer have increased significantly. In fact, in the U.S., they have tripled since the 1980s.
It is now considered the fastest-growing cause of cancer deaths in the U.S. While survival rates have improved, only 1 in 5 people survive for longer than 5 years after diagnosis.
Often, liver cancer is diagnosed at a relatively late stage. By this point, the liver is already severely damaged, and the prognosis is usually poor. Finding a way to detect the disease earlier could significantly improve the outlook for people with liver cancer.
Recently, scientists at the University of Basel in Switzerland — led by Prof. Michael N. Hall — made some headway into this problem. Their work could help to diagnose hepatocellular carcinoma earlier and, eventually, improve treatment. Their findings were published earlier this week.
The hunt for tumor suppressors
In cancer, mutated cells grow and spread in an uncontrolled manner. Tumor suppressors are anti-cancer proteins that halt this out-of-control cell growth. In cancer cells, tumor suppressors do not work as they should.
On the hunt for these elusive tumor-fighting molecules, the researchers concentrated on a mouse model of hepatocellular carcinoma.
They analyzed more than 4,000 distinct proteins in tumor tissue and compared them with healthy tissue. One protein stood out from the crowd: histidine phosphatase LHPP.
First study author Sravanth Hindupur notes, “It is striking that LHPP is present in healthy tissue and completely absent in tumor tissue.”
They found that without LHPP, tumor growth was promoted in the mice, and survival rates dropped. Conversely, by reintroducing the genetic information for LHPP, tumor growth was prevented and liver function was maintained.
The researchers also believe that LHPP might be useful as a biomarker for liver cancer. And, if this is the case, the disease could be caught earlier and treated more effectively.
In order to further investigate this relationship, the scientists measured LHPP in human liver cancer patients. Hindupur explains, “Similar to the mouse model, we also saw a striking decrease in LHPP levels in tumors of patients with liver cancer.”
They also showed that life expectancy and the severity of the disease both correlated with LHPP levels. In individuals who had no measurable LHPP at all, life expectancy was 2 years shorter. So, LHPP may also play a key role in assessing the severity of each specific case of liver cancer.
The question of phosphorylation
A protein can be phosphorylated after it has been produced. This means that a phosphate group is added to it. Phosphorylation affects the way in which a protein works — for instance, activating or deactivating it.
Although this type of chemical reaction is known to be important in a range of diseases, including cancer, it has proven difficult to study until fairly recently.
“Tony Hunter, from the Salk Institute in the U.S., has provided us with new tools to analyze histidine phosphorylation. We have now been able to visualize a whole new layer of complexity in tumor formation.”
Sravanth Hindupur
LHPP is a phosphatase that removes phosphate groups from the amino acid histidine in proteins. If LHPP is absent, there is an overall increase in the levels of phosphorylation. This triggers pathways that lead to uncontrolled cell growth and proliferation, thereby encouraging tumor growth.
The researchers hope that their findings will help to diagnose liver cancer sooner so that treatment can begin earlier.
It is also possible that LHPP has a hand in other types of cancer, so its potential benefits may stretch to other cancers over time.