A team of cancer researchers from the Rice University, from the United States, discovered the genetic principles through which cancerous cells decide when and whether or not to metastasize and invade the other parts of the organism. According to their paper, which was recently published in the early edition of the journal Proceedings of the National Academy of Sciences, there is a genetic switch that can be set either on “on”, “off”, or somewhere in between. The research team says that their finding sheds new light on previous study results that were confusing, while also opening new directions towards cancer therapies.
According to the co-author of the study, professor Eshen Ben-Jacob, cancerous cells have a very complex behavior. Professor Ben-Jacob and his colleagues reveal a novel theory about the behavior of the mRNAs’ involvement in the decision-making circuits of the cancerous cells. For their study, the research team used a new framework. In order to test this new framework, they used the behavior of the genetic circuit that regulates the transition between the mesenchymal and epithelial states of cells. The two transitions are known as EMT (epithelial-mesenchymal transition) and MET (mesenchymal-epithelial transition), and are vital to embryonic development and wound healing.
Considered to be a hallmark for cancer metastasis, the EM transition is also used by the cancerous cells in order to break away from the initial tumor location, and migrate to other tissues from the organism. In order to find new ways to block metastasis, the research team conducted more than 20 studies about the genetic circuits involved in the activation of the EM transition. One of the clearest findings from precedent papers show that the key to EM and ME transitions is a two-component genetic switch. This switch contains two pairs of proteins. The first pair of proteins are known as SNAIL/miR34, while the second pair is known as ZEB/miR200.
Both protein pairs are mutually inhibitory. This means that if one of the proteins from the pair is present, it inhibits the production of its paired protein. For the mesenchymal state of the cell, both the ZEB and SNAIL proteins are present in high quantities. In the epithelial cellular state, both microRNA proteins are found in high levels. According to Ben-Jacob, their study model reveals that both SNAIL and miR34 proteins act as an integrator for the circuit. The levels of the SNAIL protein are responsible for activating ZEB and inhibiting miR200. Due to the fact that the ZEB protein has an ability to activate itself through a positive feedback loop, the cell is capable of keeping an average level of all four proteins.
Ben-Jacob suggests that this circuit supports the metastasis of cancerous cells by enabling them to migrate as a group, while also giving the cells properties that allow them to evade the person’s immune system. He concluded that the results of the study might allow further research on cancer therapies that would outsmart this three-way switch. Furthermore, the results of the current study correspond with the results of precedent studies on bacteria lead by professor Ben-Jacob and his collaborators.