Regulation and control of the body and its processes are overseen by electrochemical signals across synapses, the dynamic spaces between nerve cells. Now, two studies from researchers at UT Southwestern Medical Center shows cancer cells can repurpose tools of neuronal communication to fuel aggressive tumor growth and spread. The team states they found cancer cells are taking a page from the neuronal signaling playbook to maintain beneficial signals, dampening the harmful ones. The first study is published in the Proceedings of the National Academy of Sciences (PNAS) and the second, opensource, study is published in the journal Developmental Cell.
Previous studies show clathrin-mediated endocytosis (CME) constitutes the major pathway for signaling in eukaryotic cells, including cancer cells. As such, CME regulates signaling from cell-surface receptors, however, just how these specific signaling receptors regulate the CME machinery remains an open question. The current studies show dynamin1 (Dyn1), a protein once thought to be present only in nerve cells of the brain is also found in aggressive cancer cells.
The current studies show in neurons, Dyn1 helps sustain neural transmission by causing rapid endocytosis, the uptake of signaling molecules and receptors into the cell, and their recycling back to the cell surface. The lab explains these processes ensure the neurons keep healthy supplies at the ready to refire in rapid succession, amplifying or suppressing nerve signals as necessary. Results show aggressive cancer cells usurp the mechanisms neurons use for the rapid uptake and recycling of neural transmitters. Data findings show instead of neural transmitters, the cancer cells use Dyn1 for rapid uptake and recycling of EGF (epidermal growth factor) receptors, known drivers of breast and lung cancers.
The group states in order to thrive, cancer cells must multiply faster than nearby noncancerous cells, with EGF receptors enabling them to do so. They go on to add cancer cell survival is another factor in disease progression. In the PNAS study data findings show aggressive cancer cells have adapted neuronal mechanisms to thwart a key cancer-killing pathway. Specifically, aggressive cancer cells appear to have adapted ways to selectively activate Dyn1 to suppress death receptors signaling to avert cancer cell death.
The PNAS study notes the aggressive cancers use a signaling pathway to increase the activity of EGF and also turn on Dyn1 pathways to suppress cancer death. They go on to stress less aggressive cancers respond to forms of chemotherapy that repress EGF signaling and/or die in response to the TRAIL-DR pathway. However, aggressive lung and breast cancer cells have adapted ways to commandeer the neuronal mechanisms identified in these studies.
The team surmises their studies show some cancer cells repurpose tools that neurons take advantage of to get a competitive advantage over nearby normal cells. For the future, the researchers state this research will someday lead to improved strategies to fight the most aggressive cancers.
Source: UT Southwestern
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