Caught in the Act: Proteins Responsible for Metastasis
The research by Assoc. Prof. Nurhan Özlü and PhD student Zeynep Cansu Üretmen Kagıalı of Koç University has identified proteins that play a role in the processes that allow cancerous cells to gain the ability to metastasize.
By: Koc University
Close to 90 percent of cancers developing in the human body are observed in epithelial cells. Özlü and her team began their research by studying more than 600 proteins to understand the roles they play in the transition from epithelial to mesenchymal cells.
When epithelial cells, which are immobile, stable and connected to other cells, turn into cancerous cells, they no longer want to be bound to their place of origin, and tend to metastasize in other areas. To do this, they have to be mobile. They abandon their epithelial origin, which gives them the characteristic of "stability", and transition into the mesenchymal cell type, which gives them mobility and allows them to metastasize. With this newly gained mobility, they can be transported to other organs and metastasize, where they can "change their identity" once again and turn into their original epithelial state.
To understand this mechanism, Özlü and her team took human breast epithelial cells and by using one of the transition factors that play a role in epithelial-mesenchymal transition and control gene expression, they turned the cells into mesenchymal cells. Next, they built a profile of the protein differences between the epithelial and mesenchymal states of the same cells. Narrowing down the proteins to 20 at the end of their research, they observed that some proteins were very dominant in the epithelial state, whereas others were dominant in the mesenchymal.
Focusing on the proteins DNAJB4 and CD81 that showed an increase in the mesenchymal state, the team injected cells, in which the expression of these two proteins was suppressed, into mice. The tumor sizes in the animals who were injected with the control cells were significantly larger than those who were injected with the cells with the two suppressed proteins.
For the article https://www.mcponline.org/