Recently, in a research report published in the international journal of Scientific Reports, scientists from the Russian Far Eastern Federal University and other institutions used the developing eyes of fruit flies as a detection platform to conduct research and found that the overproduction of a protein called RPS-12 seems to induce triple-negative breast cancer and certain malignant tumors. When the embryo develops, this protein can indirectly turn on an important intracellular signaling pathway.
Based on the results of this article, scientists have taken another step forward in the development of tumor-targeted therapies. The idea of this therapy is to identify targeted proteins that play a guiding role in tumor initiation or progression. In order to inhibit the growth of tumors while minimizing damage to healthy cells; using cDNA libraries derived from Drosophila and triple-negative breast cancer patients, researchers have launched a large-scale screening of potential new human oncogenes. That is, genes that can activate cancer transformation elements after mutation. In order to find potential targets, the researchers inserted genes found in human tumors into the genome of Drosophila so that they could drive the wrong expression of these genes in insect eyes. In addition, researchers have discovered potential defects in the development of sensitive organs.
When the human protein RPS-12 was transplanted, the eyes of fruit flies began to shrink and acquired a mirror-like appearance. Drosophila genes correspond to WNT genes, and WNT genes induce signal pathways of the same name in the human body. The activity of the WNT signaling pathway is essential for human development in the embryonic stage, but it is shut down in the later stage. Mutations or epigenetic changes can restart the signaling pathways in the adult body. After that, the initial healthy cells will begin to proliferate on a large scale. This is triple-negative breast cancer and other forms of cancer (colon, liver, and ovarian cancer). Etc.) will continue to evolve.
The researchers pointed out that the smooth eye phenotype appeared because the human RPS12 gene in the eyes of Drosophila would over-activate the WNT/wingless signaling pathway. Too much RPS12 protein would stimulate the existence of active forms of wingless protein, and will spread long distances in the tissue and reach more distant cells. Conversely, a reduction in RPS12 levels will also reduce the production of such as wingless proteins.
Researcher Vladimir Katanaev pointed out that wingless-WNT family proteins are very sticky, and their natural distribution in body tissues is very limited, while the level of long-distance migration is strictly controlled. WNT is an example of morphogens, which are substances produced at specific locations during embryonic development, which can also diffuse through tissues to form a concentration gradient. Taking human hands as an example, the palms, elbows and shoulders are formed by cells in response to different concentrations of WNT morphogens.
The special mechanism responsible for the formation of WNT forms can also spread over long distances in tissues. One of the mechanisms that was studied earlier by researchers is based on the protein reggie-1/fotillin-2. Later researchers will further study to reveal whether this protein is more suitable for therapeutic targeting.
About 70%-80% of the genes responsible for the occurrence of human diseases have homologous genes in the body of Drosophila. From an evolutionary perspective, these genes are actually the same, but there are some separate sequences in humans and fruit flies.
The development of Drosophila eyes is very complex and contains multiple stages. During the multiple stages of its development, a variety of signaling pathways and cellular mechanisms are in an active state. Based on this, scientists speculate that once any human cancer cells are transplanted into the fruit In fly eyes, it interferes with the development of organs; a fruit fly whose eye is affected will survive until adulthood, which means that the developmental disorders exhibited by fruit flies can be easily observed by observation with a microscope.
Finally, the researchers stated that their research goal is to find new human oncogenes through the fruit fly eye screening platform. The final test of the first phase has been carried out in 2020, and tconstruction of an extensive genetic library may help scientists conduct research to find the components and key mechanisms involved in cancer.
