Do human embryos and cancer have the same fuse?

At the moment of fertilization, the genes in the fertilizing sperm and egg cells are switched off. In order for a new embryo to develop, they have to be turned on – but how?

The answer is unknown, which seems remarkable for such a fundamental event early in embryonic life, and for decades it was thought that genes in human embryos were silent for several days after fertilization. However, recent evidence shows that they turn on almost instantly.

Now that this is recognized, scientists may have created the first model showing how the switch works to initiate embryonic development.

The model was developed by Professor Tony Perry from the University of Bath’s Department of Life Sciences with colleagues Dr. Maki Asami, also in Bath, and Dr. Brian Lam and Professor Giles Yeo from the University of Cambridge. Her work will be published this month Trends in cell biology.

The model suggests that the myriad events that accompany fertilization act synergistically to turn on embryonic gene expression. To emphasize that the change takes place at the beginning of development, the track borrows from Dylan Thomas’ “Under Milk Wood”: “To begin at the Beginning”.

Professor Perry and colleagues have extended the model to predict something amazing: that the switch that triggers embryo formation can also trigger cancer.

The beginning of cancer and embryonic life

By the time cancer is diagnosed, the disease is often at an advanced stage, and in some cases time is running out. We know little about how many cancers start. It can be like lighting the blue paper of a firework long gone when you see the sparkling color palette. How can we discover the nature of this fuse so that once it’s lit, we can spot it and extinguish it before cancer develops?

This is where a better understanding of the beginning of embryonic life comes in. The genes in an embryo need a switch to get going after fertilization, like the tactile paper in cancer.

Professor Perry and his team previously found that the switch in embryos contains genes called oncogenes that play a key role in cancer.

Many processes and actors are involved in embryonic development whose role we do not yet understand. For example, we don’t know how the starter switch is activated.

“The switch that turns on embryonic gene expression is likely related to changes in the packaging of the embryonic genome, called epigenetic changes, but we don’t know what these changes are or how they are controlled,” Professor Perry said. How can this incomplete idea of ​​embryos be used to understand cancer?

Understanding how cancer develops with the help of embryos

The process of fertilization is predictable and the formation of a new embryo (e.g. a mouse embryo) can be studied at all stages in one dish. This does not apply to cancer, the origin of which cannot yet be studied in the controlled environment of a laboratory. Studying embryos allows us to identify the embryonic switch and uncover how it is activated. This will show us where to look to shed light on the origin of cancer: the blue touch paper light up.

‘This approach is promising as we currently have no way to study the initiating events of cancer,’ said Professor Perry.

“In molecular terms, we don’t even know what the blue touch paper looks like. Understanding the switch that starts a new embryo provides an experimental platform to unveil how the fuse lights in cancer.”

The idea is still in its early stages, but it starts with a model of how healthy embryos are formed naturally: to start at the beginning. If correct, the model will open a new and usable window into the processes that trigger cancer long before a clinical disease is diagnosed.

In due course, this promises to unveil new diagnostic markers that can be used to anticipate and prevent cancer.