Researchers at Mayo Clinic (a medical and research center) have identified a specific signaling protein that stimulates the growth of pancreatic cancer cells. results published In the journal Cell Reports.
Scientists explained that tumors grow in a nutrient-poor environment, so cancer cells have to reorganize cellular metabolism to meet their needs. One way to obtain energy is to stop lysosomes, membrane vesicles containing digestive juices. Lysosomes break down proteins, lipids, and other substances that cells need to grow. Previous studies have shown that increased lysosome activity is a sign of the development of various types of cancer.
This information led researchers to carefully examine the properties of lysosomes in pancreatic cancer cells in the presence of one of the variants of the KRAS oncogene, whose mutations have the potential to transform normal cells into malignant cells. To find out what the differences were, the scientists compared lysosomes from oncogenic KRAS cells from pancreatic cancer cells with lysosomes from cells with the normal variant of the gene.
Among the 52 proteins they found to be altered on the surface of lysosomes in pancreatic cancer cells, a protein called cytokinesis promoter 8 (DOCK8) was isolated. DOCK8 is normally found in healthy immune cells. It helps them move through the body and fight infections. It turns out that the mechanisms that DOCK8 can reproduce to help immune cells can be triggered to destroy the extracellular environment around the cancer cell. This helps tumor cells spread faster.
To confirm their theory that DOCK8 plays a role in tumor progression, the team used the CRISPR gene editing tool to knock out DOCK8 from pancreatic cancer cells. The preclinical model showed that lysosomes lacking DOCK8 moved more slowly, slowing tumor growth and reducing metastasis.
The scientists hope that their discovery will contribute to the development of new treatments for pancreatic cancer based on inhibition of DOCK8 activity.
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