Can Cancer Cells be Programmed Back to Normal?

In a recent study published in Nature Cell Biology, researchers at the Mayo Clinic described a way in which cancer cells could potentially be programmed back into normal cells. Their findings were stimulated by the fact that proteins that hold cells together, or adhesion proteins, interact with the Microprocessor complex, which mediates the production of microRNAs (miRNAs).

Their research showed that when normal cells come into contact with each other, certain miRNAs are prompted to suppress cell growth by downregulating the expression of genes involved in cell growth. However, in cancer cells, where adhesion is disrupted, the expression levels of these miRNAs are affected and the cells grow uncontrollably. Their study also answered a long-standing question in the field — why are adhesion proteins, specifically E-cadherin and p120, which are essential for the normal formation of cellular junctions and are considered to be tumor suppressors, present in tumor cells and seemingly required for their progression?

The scientists hypothesized that these adhesion proteins had dual functionality — on one hand, they were responsible for the proper formation of cellular junctions but on the other, they drove tumor growth and progression. They found evidence to support their theory, discovering that a protein called PLEKHA7, which localizes to the apical surface of epithelial cells, is responsible for regulating the behavior of these adhesion proteins. Specifically, in normal cells, PLEKHA7 recruits the Microprocessor complex to the apical surface of epithelial cells and regulates certain miRNAs to control the expression levels of E-cadherin and p120 and hence cell growth. However, when the PLEKHA7-Microprocessor complex system is disrupted, which is common in the early stages of cancer progression, the miRNAs are misregulated and, in turn, are not able to regulate E-cadherin and p120, promoting uncontrolled cell growth. Work is now being carried out to determine whether restoring the levels of these miRNAs can reverse the effects on cell growth; the initial experiments are proving to be quite promising.

Source: Mayo Clinic