Journal News

Unlocking how cellular proteins control cancer spread

New finding may help focus the search for anti-cancer drugs
Erin Matthews
By Erin Matthews
Aug. 29, 2020

A new insight into cell signals that control cancer growth and migration could help in the search for effective anti-cancer drugs. A McGill University-led study reveals key biochemical processes that advance our understanding of colorectal cancer, the third most common cancer among Canadians.

Using the Canadian Macromolecular Crystallography Facility beamline at the Canadian Light Source at the University of Saskatchewan, scientists from McGill University 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 Journal of Biological Chemistry, 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.

JBC-McGill-paper-700x506.jpg
Kalle Gehring et al./JBC
Immunofluorescence images of HEK293 cells showing proper localization of transfected PRL3 mutants except C104N.

"These enzymes were first seen in liver cells that were activated to start growing, so somehow they act as a growth signal," said McGill biochemistry professor and corresponding author 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. "What 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," said Gehring.

The team's 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's 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's 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.

 

Enjoy reading ASBMB Today?

Become a member to receive the print edition four times a year and the digital edition monthly.

Learn more
Erin Matthews
Erin Matthews

Erin Matthews is a freelance science writer with a focus on health, biology and biotechnology. She has been the summer communications assistant at the Canadian Light Source for the last two seasons.

Get the latest from ASBMB Today

Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.

Latest in Science

Science highlights or most popular articles

Calcium channel linked to cancer drug resistance
Journal News

Calcium channel linked to cancer drug resistance

June 12, 2025

Researchers discover a protein associated with carboplatin-resistant retinoblastoma, suggesting this protein could be a promising therapeutic target. Read more about this recent Journal of Biological Chemistry paper.

Host fatty acids enhance dengue virus infectivity
Journal News

Host fatty acids enhance dengue virus infectivity

June 12, 2025

Researchers in Germany find that viral replication depends on host enzymes that synthesize lipids, revealing potential metabolic targets for antiviral intervention. Read more about this recent Journal of Biological Chemistry paper.

Antibodies inhibit hyperactive protein disposal
Journal News

Antibodies inhibit hyperactive protein disposal

June 12, 2025

Researchers at the University of California, San Francisco, identify an enzyme inhibitor, offering new tools to study diseases like cystic fibrosis, neurodegeneration and cancer. Read more about this recent Journal of Biological Chemistry paper.

Scientists find unexpected correlation between age and HDL-C levels
Journal News

Scientists find unexpected correlation between age and HDL-C levels

June 3, 2025

In a 30-year multicenter study, researchers determined what factors predict HDL-C concentration. In their analysis, they found that HDL-C levels grew with increasing age and physical activity.

Butter, olive oil, coconut oil — what to choose?
Journal News

Butter, olive oil, coconut oil — what to choose?

May 28, 2025

Depending on the chain length and origin of the fat, regular fat consumption changes the specific makeup of fats in bloodstream and affect mild to severe cholesterol patterns. Read about this recent Journal of Lipid Research study.

Computational tool helps scientists create novel bug sprays
Journal News

Computational tool helps scientists create novel bug sprays

May 20, 2025

Rapid discovery of mosquito repellent compounds is enabled through a novel screening platform that combines both computational modeling and functional screening.