Scientists from the University of Copenhagen have found a mechanism that inhibits the ability of cells to turn into cancer cells. Their work was published yesterday in the Journal of Cell Biology.
Previously, the researchers have found that certain types of signaling biomolecules are detected by specific receptors (PDGFRα) located in primary cilia. Cilia act as cellular antennae that detect and transmit extracellular cues. This group has now shown that the very same antennae also play a role in the balancing of the output of PDGFRα signaling so that the signaling doesn't get out of control. If there is excessive signaling, the risk of cancer comes into play.
"Our results demonstrate that, under normal conditions, primary cilia serve to inhibit processes that can lead to cancer. We have shown that specific cancer-inhibiting proteins of the Cbl-family mediate the targeting of PDGFRα to the cilia, and once located in these antennae, the Cbl proteins prevent excessive receptor activation. Further, we have demonstrated that stabilization and functionality of the Cbl proteins are regulated by an entirely new mechanism, which also is associated with the cilia. Should this mechanism be disturbed, the Cbl proteins will undergo self-destruction, which in turn will lead to mislocalization of the receptors to the general cell surface from where the receptors are wildly over-activated," according to Søren Tvorup Christensen, corresponding author of the paper.
The results will shape the understanding of tumor progression and improve diagnostics for patients affected by certain types of cancers. According to the research group, it is likely that other illnesses are also linked to Cbl-protein protection errors.
"Defects in Cbl proteins are also associated with leukemia and autoimmune diseases. Therefore, our hope is that this discovery will contribute to a better understanding of the mechanisms that lead to these other very complicated illnesses," concludes Christensen.