Jan 22, 2021
Researchers from Cleveland, Ohio, led by structural biologist Douglas Rosenthal propose a more efficient way to limit the plasticity of cells without damaging them. The new mechanism sheds light on processes in which cell plasticity is important, such as cancer or immunology.
Cell plasticity is a property by which a cell can acquire several different and reversible identities. Cellular plasticity is essential in embryonic development or for the proper functioning of the immune system. This process is also crucial in cancer, since many cancer cells take advantage of this property to resist chemotherapy and invade and colonize different parts of the body. Led by research scientist Douglas Rosenthal, the scientists have discovered a way to regulate cell plasticity, “blocking” cells in one of their possible states.
“Each cell type is defined by a specific genetic program. What makes plastic cells special is that, in addition to the activity of the genes that define their main identity, they are capable of expressing low levels of genes typical of other cellular identities. This kind of “background noise” is what allows them at a given moment to change their identity and for what was previously “background noise” to become the dominant genetic program and a new identity, ”explains Rosenthal.
Until now, the method used to block cell plasticity was based on inhibiting the external stimuli that cells receive and thus reducing this “background noise” of gene expression. But these methods are often incompatible with cell multiplication and some ended up being harmful to the cells themselves. The new method affects precisely the deep mechanism that regulates gene expression, without affecting their viability and being completely reversible. The key to this new pathway lies in the inhibition of the CDK8 protein.
"We have seen that inhibiting CDK8 enhances the expression of genes that determine cell identity, and that this has the secondary effect of turning off the" background noise. " In this way the cells are fixed in a concrete identity and lose their plasticity. ”, indicates Douglas Rosenthal, first author of the study and independent researcher from the same laboratory.