How embryonic genes are related to cancer and fibrosis
August 5, 2022

The last of the extraordinary conferences of the 2022 edition of the UCM Summer Courses , has allowed Ángela Nieto Toledano , a researcher at the CSIC Institute of Neurosciences , to hear about the studies that have been carried out since 1994 that relate fundamental programs in embryonic development with different diseases associated with aging such as cancer and fibrosis .

Ángela Nieto assures that in Biology there is a recurring question that is “how an individual originates and organizes from a single cell”. From that moment, the ideal situation is reached, which is that of the young adult, which is “when everything is in its place and works perfectly, because from then on, due to homeostasis, we degenerate and many pathologies associated with age appear. including ageing.

It has been known since the 19th century that embryonic development is similar in all animals , so much so that only experts could identify the species to which a specific embryo belongs. That, according to the speaker, is not just a curiosity, but ” means that there are a series of general mechanisms that all animals use to give rise to their forms and functions .”

During this development, “a spectacular tissue appears, which is the neural crest” , which is the origin of many cells in our body, practically all the cells of the peripheral nervous system, almost all the pigmented cells, those of the craniofacial skeleton, the odontoblasts… What in principle are static cells migrate and with a kind of “switches” they express different genes in each of the cells , and that is what is known as epithelial-mesenchymal transition.

These genes, according to Nieto, have a regulatory mission, in many cases of more than 500 genes, but “it is not important because it is very spectacular, but because it is at the center of many processes, such as embryonic development, morphogenesis and homeostasis where everything works relatively well”. The epithelial-mesenchymal transition is also involved in wound healing and in the partial regeneration of tissues , which “has been lost throughout evolution, but which remains in the liver, for example, and serves to better understand how design strategies to engineer tissue regeneration”. Something that, according to the researcher, “is at a very important moment of study and that will give good results in the coming years.”

The dark side

The other side of the coin of this process implies that these switches do not always work well and in pathological situations, of genetic and epigenetic origin, they turn on again in adult life and have an enormous impact on diseases such as cancer and fibrosis .

The first modern evidence that this mechanism was important in embryonic development was obtained in 1994 and now, two decades later, it is already a recognized hypothesis in the scientific community, especially in its role in the development of cancer and metastasis. The next few years will be a source of knowledge and new therapies that are already being developed in different parts of the world .

Nieto explains that in cancer cells spread, nest and form another tumor, and that is what is known as “ metastasis, which is the cause of death in cancer patients in more than 90% of cases ”. The first thing that was thought of, as a possible therapy, was to find inhibitors of the genes that turn on this process , which is conceptually very correct, but thanks to experimentation it has been understood that it was not so simple. This is so, because many tumors carry out cell dissemination at a very early time, before diagnosis, so the therapeutic strategy is not a good idea, because expansion would be prevented, but already disseminated tumor cells would stop, nest and form more metastasis. There are cancers with a poor prognosis, such as pancreatic cancer, that shed cells even before a primary tumor can be detected.