Scientists identified novel cellular mechanism that can lead to cancer metastasis

Understanding of how cells alter their communication.


Scientists at the Virginia Tech Carilion Research Institute have gathered new insights that may lead to better understanding of how cells alter their communication with one another during development, wound healing, and the spread of cancer.

This insight can offer information to scientists on how an individual cell can dynamically modulate its synthesis of proteins from existing genetic instructions.

During the process of epithelial-mesenchymal transition or EMT, when tissue grows or heals, its outer layer of epithelial cells takes on characteristics that allow cells to migrate, change their size and behavior, and act as other cell types. These cells are useful for repairing.

James Smyth, an assistant professor in the VTCRI Center for Heart and Regenerative Medicine Research at the VTCRI said, “The problem is that EMT is also activated in various disease processes, such as fibrosis and cancer metastasis. Fortunately, these cells are very amenable to manipulation. We’ve developed a powerful new tool to study this process to help us get to the heart of cancer metastasis. We can observe cancer cells change their communication with each other to become more invasive, to separate, and to disperse throughout the body.”

“Researchers will also be able to use their techniques to better understand cellular responses to injury and disease in other pathologies, such as cardiac disease, as well.”

Connexin 43 protein plays a vital role in cardiac cells. When six connexins 43 proteins come together, they form channels called gap junctions through which cells communicate. Connexin 43 is synthesized from the message encoded in RNA that has read out the DNA code. The RNA can also encode for smaller pieces or fragments of connexins 20k, that ensure gap junction formation.

Smyth said, “It was thought that the amount of RNA correlated with the amount of connexin protein, but we now know that it’s much more complicated than that. The point of protein synthesis for translation is tightly regulated by the cell, and it is dynamic, changing with development and with the disease.”

Scientists found that RNA and protein synthesis of connexin increased during EMT, but the number of gap junctions on the surface of the cell did not increase as expected.

Scientists later focus on understanding the mechanisms that regulate cell-to-cell interaction in cancer and how deregulated intercellular communication can lead to cancer progression through EMT.

Samy Lamouille, a research assistant professor at the VTCRI said, “In this study, we found the formation of gap junction structures that allow cells to communicate was disrupted during EMT despite an abundance of connexin 43.”

The cell makes the 20k connexin fragments to direct the full-length connexin 43 to the surface of the cell. Scientists hypothesized that the connexin (20k) fragments were being suppressed during the internal translation process of protein synthesis.

By using the VTCRI’s super resolution microscope, scientists found that the full-length connexins were arrested in the cell’s Golgi apparatus, which acts as a packaging plant for proteins heading to the surface of the cell. To counteract the suppressed expression of 20K connexin fragments, they used a lentivirus vector to cause the cells’ RNA to make 20k connexin, thereby rescuing the full-length connexin 43, the formation of gap junctions, and normal cellular communications.

Scientists are now planning to apply this study on cardiovascular disease. The researchers published their results in Molecular Biology of the Cell, a journal published by the American Society for Cell Biology.

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