Regulation and control of the body and it processes are controlled by electrochemical signals across synapses, the dynamic spaces between nerve cells. Now, two studies from researchers at UT Southwestern Medical Center show that cancer cells can repurpose tools of neuronal communication to fuel aggressive tumour growth and spread. The team state they found that cancer cells are taking a page from the neuron’s signalling playbook to maintain certain beneficial signals and to squelch signals that would harm the cancer cells. 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 that clathrin-mediated endocytosis (CME) constitutes the major pathway for uptake of signalling receptors into eukaryotic cells, which includes cancer cells. As such, CME regulates signalling from cell-surface receptors, how specific signalling receptors reciprocally regulate the CME machinery remains an open question however. The current studies show that dynamin1 (Dyn1), a protein once thought to be present only in nerve cells of the brain and spinal cord, is also found in aggressive cancer cells.
The current studies show that, in neurons, Dyn1 helps sustain neural transmission by causing rapid endocytosis, which is the uptake of signalling molecules and receptors into the cell, and their recycling back to the cell surface. The lab explain that these processes ensure the neurons keep healthy supplies at the ready to refire in rapid succession and also help to amplify or suppress important nerve signals as necessary. Results show that aggressive cancer cells usurp the mechanisms which neurons use for the rapid uptake and recycling of neural transmitters. Data findings show that instead of neural transmitters, the cancer cells use Dyn1 for rapid uptake and recycling of EGF (epidermal growth factor) receptors, mutations in EGF receptors are drivers of breast and lung cancers.
The group state that in order to thrive, cancer cells must multiply faster than nearby noncancerous cells, and EGF receptors enable them do this. They go on to add that cancer cell survival is another factor in disease progression. In the PNAS study data findings show that aggressive cancer cells have adapted neuronal mechanisms to thwart a key cancer-killing pathway triggered by activating death receptors on cancer cells. Specifically, aggressive cancer cells appear to have adapted ways to selectively activate Dyn1 to suppress death receptors signalling to avert cancer cell death.
The lab note that the aggressive cancers use a signalling pathway to increase the activity of EGF and also turn on Dyn1 pathways to suppress cancer death. They go on to stress that less aggressive cancers respond to forms of chemotherapy which repress EGF signalling 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 surmise their studies show that some cancer cells repurpose tools which neurons use in order to get a competitive advantage over nearby normal cells. For the future, the researchers state that this research will someday lead to improved strategies to fight the most aggressive cancers; they are now conducting research to identify Dyn1 inhibitors as potential anticancer drugs using a 280,000-compound library.
Source: UT Southwestern
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