Protein that protects against cell suicide during normal development could inspire new cancer target

09 October 2014

Under normal circumstances (top), cells that become detached from epithelial sheets are eliminated by apoptosis, or cell suicide. The protein identified in this study, Schnurri, can stop this apoptosis when it’s not wanted. Inhibiting Schnurri may offer a target for some cancers, in which normal apoptosis doesn’t occur as it should (bottom).

Image: Under normal circumstances (top), cells that become detached from epithelial sheets are eliminated by apoptosis, or cell suicide. The protein identified in this study, Schnurri, can stop this apoptosis when it’s not wanted. Inhibiting Schnurri may offer a target for some cancers, in which normal apoptosis doesn’t occur as it should (bottom).

Scientists at the Medical Research Council's National Institute for Medical Research (NIMR; now part of the Francis Crick Institute) have identified a protein called Schnurri that protects some epithelial cells against apoptosis, or cell suicide, in fruit flies. 

The protein is also found in humans and so the research has implications for many diseases that are caused by a failure to eliminate defective cells, such as cancer.

Dr Jean-Paul Vincent of NIMR explained: "Most tissues are made of epithelia, sheets of cells that adhere to each other. Epithelial cells line the surfaces and cavities of our bodies - such as our skin and glands. When cells become detached from these sheets, they activate a stress pathway called JNK that leads to their elimination by apoptosis, a type of ordered cell suicide.

"The same stress pathway is required for epithelial cells to undergo migration, for example during the movement that brings two epithelia together in an embryo and allows it to develop its shape. In developmentally programmed situations like this, the JNK pathway does not lead to cell death. This suggests that there is a protective mechanism at work."

In their current study, the researchers showed that, in the fruit fly embryo, this protective mechanism involves a protein called Schnurri, which is also found in humans.

The NIMR researchers worked with colleagues from the University of Freiburg and the European Laboratory of Molecular Biology in Heidelberg, both in Germany. The team used a combination of genetic and molecular techniques to decipher the regulation of reaper, a key gene involved in cell death in the fruit fly. They then studied mutant fruit flies lacking the Schnurri protein and, using cutting-edge 3D imaging, found that cells at the edge of migrating epithelial layers undergo excessive cell death.

Dr Vincent said: "Since Schnurri is present in humans, our findings could be relevant to many diseases that are caused by a failure to eliminate defective cells, including cancer.  It is conceivable for example that excessive activity of Schnurri might protect cells that should otherwise die."

"As a first step to address this possibility, it will be important to determine whether Schnurri also plays a pro-survival role in mice. Our study illustrates how organisms such as the fruit fly that are simple and relatively easily manipulated genetically can be used to decipher complex gene interactions and thus pave the way for targeted investigation in higher organisms."

The paper, The Dpp/TGFb-Dependent Corepressor Schnurri Protects Epithelial Cells from JNK-Induced Apoptosis in Drosophila Embryos, is published in Developmental Cell.

  • A protein called Schnurri that protects some epithelial cells against apoptosis, or cell suicide, could be a target for treating disesases caused by a failure to eliminate defective cells, including cancer, according to new research.
  • The protein was identified by a study in Drosophila melanogaster (a fruit fly), which has been studied by developmental biologists and geneticists as a model organism for over a century. However the protein is also found in humans, indicating that the findings could provide a starting point for studying its role in human diseases.