Mayo Clinic researchers have made a significant breakthrough in understanding how pancreatic cancer, one of the deadliest cancers in the U.S., spreads throughout the body.
This new discovery centers around a cell-signaling protein, opening up potential avenues for therapeutic interventions.
The study, led by Gina Razidlo, Ph.D., and published in Cell Reports, delves into the process of metastasis—the way cancer cells spread from their original site to other parts of the body.
The researchers focused on pancreatic cancer cells, particularly those driven by mutations in the KRAS gene, a common oncogene in pancreatic cancer.
Cancer cells, including those in pancreatic tumors, adapt their metabolism to thrive in nutrient-poor environments.
They do this by altering lysosomes, which are like the cell’s stomach, packed with enzymes that break down proteins and nutrients. Enhanced lysosome activity is known to be a feature of various cancers.
Dr. Razidlo and lead author Omar Gutierrez Ruiz, Ph.D., conducted a detailed study of lysosomes in pancreatic cancer cells.
Collaborating with Mayo Clinic’s Proteomics Core, they discovered that among 52 proteins altered on the lysosomes’ surface in cancer cells, one particular protein stood out: dedicator of cytokinesis 8 (DOCK8).
DOCK8 is typically found in healthy immune cells, where it helps navigate dense tissues. But in pancreatic cancer cells, DOCK8 was found on lysosomes, playing a different role.
It creates protrusions, akin to tiny arms, enabling cancer cells to worm through and alter their surroundings, aiding in metastasis.
To understand DOCK8’s role in cancer spread, the team used the Mayo Clinic’s Center for Cell Signaling in Gastroenterology to observe pancreatic cancer cells.
They witnessed DOCK8 working through lysosomes to break down the area around the cancer cell, facilitating its movement and spread.
To test DOCK8’s influence on tumor progression, the researchers used CRISPR gene editing to eliminate DOCK8 in pancreatic cancer cells.
In a preclinical model, they observed slower lysosome movement, reduced tumor growth, and decreased metastasis in DOCK8-depleted cells. Furthermore, they found DOCK8 present in about 20% of pancreatic cancer patients studied.
This discovery of DOCK8’s role in pancreatic cancer metastasis marks a crucial step in understanding and potentially combating this aggressive form of cancer.
By targeting DOCK8, there’s potential to develop treatments that could prevent or slow down the spread of pancreatic cancer, offering new hope for patients battling this challenging disease.
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The research findings can be found in Cell Reports.
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