MYC gene with significant influence on embryonic development
The actual function of the cancer gene MYC remained unclear for a long time. Scientists at the German Cancer Research Center (DKFZ) in Heidelberg have now found out that MYC controls the development of stem cells in the early embryonic phase, but can promote the formation of metastases in the later stage through the same effect. The researchers published their results in the specialist magazine "Cell".
According to the DKFZ, the following applies to many types of cancer: the more MYC they produce, the more aggressively the tumors grow. However, the scientists had noticed that MYC is also active in embryonic stem cells. Now Andreas Trumpp's team from the German Cancer Research Center has been able to demonstrate that the gene significantly controls the development of stem cells. In nature, the effect can be observed for deer in the form of the so-called "dormancy" or "diapause".
Reproduction adapted to the environmental conditions
"In order to give birth to their young at the best possible time, many animal species take a break when developing their embryos," explains the DKFZ. Through this so-called diapause, reproduction is adapted to the environmental conditions. For example, fawns would be "born after a gestation period of around ten months in early summer - when it is warm and the food supply for the mother is plentiful." According to the researchers, six months would actually be sufficient for the development of the embryos, "but then it would come to the Mating in the late summer gave birth to the young already in winter. ”A hormone-controlled development break in the early embryos therefore extends the gestation period by nature.
Biochemical sleep state
The scientists at the DKZ and the stem cell institute HI-STEM have now been able to demonstrate that this process is controlled by the cancer gene MYC. When MYC is switched off, embryonic stem cells and early mouse embryos fall into a reversible biochemical sleep state, according to the DKFZ. However, the ability of the cells to develop into all different types of cells in the body remains unaffected. The sleeping cells remained alive and maintained their stem cell identity, the researchers emphasize. The cells would continue to have the important “stem cell factors” that enable them to differentiate themselves into the more than 200 different cell types in the body.
Function of MYC so far unclear
In order to decode the function of the MYC gene, the researchers used embryonic stem cells from mice, whose two MYC genes (c-MYC and N-MYC) could be specifically switched off, according to the DKFZ. According to the researchers, the "embryonic MYC-negative stem cells" reduced the activity of those genes that are crucial for cell division, cell growth and metabolism. The cells were put into a kind of biochemical sleep state, "which strongly reminds us of the process of diapause, which has so far been completely misunderstood," emphasizes Roberta Scognamiglio, first author of the current study. This would "put the early embryos, so-called blastocysts, into a sleep-like state without growth and almost no metabolism before implantation in the uterus".
MYC also responsible for the diapause?
To find out whether the MYC gene is also responsible for diapause, the researchers compared the activity of all genes in MYC-negative embryonic stem cells with that in pausing mouse blastocysts. In both cases, the same gene groups were inactivated besides MYC, according to the DKFZ. These were “primarily those genetics that control protein synthesis and cell growth. The stem cell factors, on the other hand, were produced unchanged, ”reports the German Cancer Research Center. If normal blastocysts in the culture dish were treated with the MYC inhibitor, they fell into a diapause-like state. When the sleeping embryos were subsequently transferred to surrogate mice, the researchers said they grew up to be normal young animals.
Completely reversible sleep state
"To initiate diapause or to put embryonic stem cells to sleep, it is sufficient to switch off the cancer gene MYC," explains Andreas Trumpp. This does not affect the potential of the stem cells. "This is a very special property of stem cells, because all other cell types die after MYC blockade," said the expert. In addition, the state is reversible. Immediately after the inhibitor was discontinued, the cells would have started to synthesize RNA, protein and DNA again and could multiply indefinitely. "After reactivating MYC, the sleeping embryos can develop into healthy animals," reports the DKFZ.
Metastatic Growth Affected by MYC?
According to the scientists, MYC presumably also has an ominous influence on cancer stem cells, especially on the sleeping metastatic stem cells. The latter could get into foreign organs during their migration through the bloodstream and come under the influence of signaling molecules, such as those that develop during inflammation. In this way, the sleepers' MYC production could be boosted again and cause them to grow into metastases. "We are now trying to develop strategies to attack such dangerous sleep cells with a MYC blockade," explains stem cell researcher Andreas Trumpp. (fp)