A surprising finding explains how a crucial cancer gene impacts cell signaling to drive aggressive cancer growth.

‘Study provides a new view to the potential role of PTEN on how cancers modulate the outside world and how aggressive they get.’

Merajver's lab at the Rogel Cancer Center worked with a Michigan Engineering team led by Allen Liu, Ph.D., and postdoctoral researcher Luciana Rosselli-Murai, Ph.D. They focused on a protein called clathrin, which impacts how metabolites, hormones and other proteins enter into a cell. Clathrin-coated pits form little indentations inwards on the surface of cells that fold in on themselves and internalize these molecules. 




In this study, published in the Journal of Cell Science, researchers looked at breast cancer cells that did not express PTEN, a protein known to be mutated or deleted in about a third of breast cancers. They found PTEN played a role in the dynamics of clathrin-coated pits. Changing these dynamics by deleting PTEN resulted in shorter-lived pits.
"The clathrin-coated pits that don't live longer than 20 seconds have historically been thought to be non-important. But we found that those are the ones important for bringing signals from outside the cell into the cell," says study author Joel Yates, Ph.D., a research scientist in Merajver's lab.
Many cancers develop because of cell signaling problems. Signals must get from outside the cell into its nucleus to produce proteins. If the signal is altered, it alters what the cell makes, which then alters how the cell grows. This study finds that the short-lived clathrin-coated pits are used to help control the signals that enter the cell. Additionally, PTEN alters the signaling of the clathrin-coated pits that make cancer more aggressive.
"Our work provides evidence that challenges the current paradigm that short-lived clathrin-coated pits are abortive structures, finding that instead they can be capable of driving signaling," says Liu, assistant professor of mechanical engineering and biomedical engineering at U-M.
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"This finding opens a new view to the potential role of PTEN on how cancers modulate the outside world and how aggressive they get. It potentially opens new lines of thinking about how to attack the cancer and prevent it from becoming more aggressive," Merajver says.
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Source-Eurekalert