Researchers have revealed the mechanisms involved in the progression of cancer cells, opening new therapeutic perspectives against pancreatic cancer.
In observing cancer cells in patients with pancreatic cancer, researchers discovered that a protein, DOCK8, was involved in the spread of the tumor. By removing it in cancer cells, they even noticed that tumor growth slowed down and metastases decreased. "Now that we know that DOCK8 regulates the metastasis process, it could potentially be a therapeutic target to prevent or stop pancreatic cancer metastases," the researchers hope.
How does cancer spread? While the question has always animated the scientific field, a team of researchers from the Mayo Clinic in the United States has just made a major discovery on how a tumor progresses and evolves into metastasis. Their work was published in the journal Cell Reports.
The analysis of lysosomes in pancreatic cancer cells
"It is notably through lysosomes [an intracellular regulation center for metabolism and signaling] that cancer cells divert metabolic pathways," the scientists recall in a statement. Filled with digestive enzymes, lysosomes function as the cell's stomach and break down proteins, lipids, and other nutrients that allow cells to grow. Previous studies have shown that increased lysosome activity is a key characteristic of various forms of cancer.
Starting from this observation, the researchers wanted to examine the characteristics of lysosomes in pancreatic cancer cells associated with KRAS gene mutations. They compared the lysosomes of cancer cells expressing the mutated oncogene KRAS with the lysosomes of cells expressing healthy KRAS, to "understand what was different."
The protein DOCK 8 involved in tumor progression
Among the 52 proteins identified that had changed on the surface of lysosomes in pancreatic cancer cells, one stood out: the protein called "Dedicator of cytokinesis protein 8," or DOCK8, whose "invasive protrusions can pass through a cell, change its structure and degrade its environment."
While DOCK8 is generally found in healthy immune cells to help them navigate and penetrate dense tissues and thus fight infection, the researchers also discovered that the protein "uses lysosomes to break down the extracellular environment around the cancer cell, which helps it spread."
To verify that DOCK8 was indeed involved in tumor progression, they even eliminated it in pancreatic cancer cells, using a gene editing tool. And they found that "lysosomes then moved more slowly, tumor growth slowed down, and metastases decreased," explains the study's lead author, Dr. Gutierrez Ruiz, who hopes in the future to make DOCK8 "a therapeutic target to prevent or stop metastases of pancreatic cancer."
