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The effect of antitumour penetrating peptides based on connexin-43 in the selective metabolic reprogramming of human glyoma stem cells

17th national competition for scientific and technical research

Metabolism and cancer

Senior Researcher : Aránzazu Tabernero Urbieta

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Research Centre or Institution : Instituto de Neurociencias de Castilla y León. Universidad de Salamanca.


Glyomas are the most common cerebral tumour and generally have a very poor prognosis. In spite of major advances in surgery, chemotherapy and radiotherapy, the average life expectancy of patients diagnosed with malign glyoma is no longer than 18 months. These tumours contain a subpopulation of cells known as glyoma stem cells or initiators. They are thought to be responsible for the recurrence of glyomas, as they have a high oncogenic potential and are resistant against chemo- and radiotherapy. Unlike the rest of glyoma, these cells survive in unfavourable environments because they reprogram their metabolism, increasing the expression of, among others, the carrier with a high affinity for glucose, GLUT3. In fact, the elimination of GLUT3 reduces the tumorigenicity of glyoma stem cells, so that it has become an interesting therapeutic strategy. Nevertheless, acting on GLUT3 in glyoma cells without affecting the neurons, which use the same carrier, is highly complex. We recently described how penetrating peptides based on the interaction between connexin-43 and c-Src specifically reverse, the phenotype of glyoma stem cells, as they reduce the expression of stem cell markets such as Sox-2 or Id1, reducing the formation of neurospheres and increasing the expression of cell differentiation markers. The general aim of this project is to determine whether these penetrating peptides or their derivatives reverse the metabolic reprogramming of glyoma stem cells, which is of key importance for tumour progression, without affecting the metabolism of healthy cells in the brain.

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