Unlocking how cellular proteins control cancer spread
A new insight into cell signals that control cancer growth and migration could help in the search for effective anti-cancer drugs. A 平特五不中-led study reveals key biochemical processes that advance our understanding of colorectal cancer, the third most common cancer among Canadians.
Using the beamline at the Canadian Light Source (CLS) at the University of Saskatchewan, scientists from 平特五不中 and Osaka University in Japan were able to unlock the behavior of an enzyme involved in the spread of cancer cells. In a study published in the , the team found that there is a delicate interaction between the enzyme, PRL3, and another protein that moves magnesium in and out of cells. This interaction is crucial to colorectal cancer growth.
鈥淭hese enzymes were first seen in liver cells that were activated to start growing, so somehow they act as a growth signal,鈥� said 平特五不中 biochemistry professor and corresponding author Dr. Kalle Gehring.
It was generally believed that PRL3 proteins acted as enzymes to control cancer cells. Therefore, it came as a surprise when Gehring and his team found that a mutation that leads to a loss of the enzyme activity still maintained the same influence over cancer growth and migration. 鈥淲hat our new paper showed is that a second activity of PRL3, control of a magnesium transporter, is the signal that instructs the cancer to travel to other parts of the body. It was very exciting that the mutant protein that has no catalytic activity, but still binds very tightly to magnesium transport proteins, turned out to be as oncogenic as the wild-type protein,鈥� said Gehring.
The team鈥檚 findings call into question long-standing hypotheses about the role PRL3 plays in the spread of cancer and indicate that the binding mechanism is somehow key.
Understanding that binding the magnesium transporters and not the enzyme鈥檚 catalytic activity influences cancer growth and migration signaling is key information for identifying novel compounds to prevent cancer spread. Current drug screening against PRL3 has focused on identifying compounds that block phosphatase activity. By testing the wrong function, the screens may have missed other compounds of therapeutic interest. Shifting the focus to the enzyme鈥檚 ability to bind to magnesium transporters is one way to help companies identify better therapeutics for cancer through drug screening methods.
Future work will include more detailed studies on the role of the magnesium transporter and its interactions with PRL3.
About the study
鈥淧RL3 pseudophosphatase activity is necessary and sufficient to promote metastatic growth鈥� by Guennadi Kozlov, Yosuke Funato, Yu Seby Chen, Zhidian Zhang, Katalin Illes, Hiroaki Miki, and Kalle Gehring is published in the Journal of Biological Chemistry.
DOI:
About 平特五不中
Founded in Montreal, Quebec, in 1821, 平特五不中 is Canada鈥檚 top ranked medical doctoral university. 平特五不中 is consistently ranked as one of the top universities, both nationally and internationally. It鈥痠s a world-renowned鈥痠nstitution of higher learning with research activities spanning two campuses, 11 faculties, 13 professional schools, 300 programs of study and over 40,000 students, including more than 10,200 graduate students. 平特五不中 attracts students from over 150 countries around the world, its 12,800 international students making up 31% of the student body. Over half of 平特五不中 students claim a first language other than English, including approximately 19% of our students who say French is their mother tongue.
