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Connecting cancer to the asymmetric division of stem cells

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In the leading edge section of Cell, C. Gonzalez (IRB Barcelona) and A. Wodarz (CMPB, Germany) review the latest articles providing new insight into the mechanisms by which loss of polarity in stem cell may lead to tumourigenesis.

The hypothesis that some tumours may arise by the transformation of stem cells has recently gained much attention. Stem cells possess an enormous developmental potential and have the unique ability to self-renew. These two features, essential for their normal behaviour during development and adult tissue homeostasis, could make of stem cells a major threat to the organism if the machinery that keeps them in check becomes defective.

Is this a plausible mechanism of tumourigenesis? Exploiting Drosophila neuroblasts as model stem cells, three papers published in the last months demonstrate that this is indeed the case. These papers show that keeping the self-renewal potential of stem cells at bay requires the tight control of the unequal segregation of cell-fate determinants in mitosis, a process that, in all likelihood, is as critical to human stem cells as it is to Drosophila neuroblasts. Furthermore, these articles have revealed a direct connection between loss of the cell-fate determinants Brat and Pros and the ectopic upregulation of specific target genes that in flies and in humans are known to control the cell cycle.

It remains to be determined whether the human homologues of the Drosophila genes involved in the control of asymmetry and cell fate work in a similar way to prevent the generation of cancer in man. However, Drosophila is showing its worth when it comes to modelling fundamental processes that are relevant for understanding human diseases.

References

  • Betschinger, J., Mechtler, K., and Knoblich, J.A. (2006). Cell.
  • Caussinus, E., and Gonzalez, C. (2005). Nat. Genet. 37, 1125–1129.
  • Lee, C.-Y., Wilkinson, B.D., Siegrist, S.E.,Wharton, R.P., and Doe,C.Q. (2006a). Dev. Cell. 10.1016
  • Reya, T., Morrison, S.J., Clarke, M.F., and Weissman, I.L. (2001). Nature 414, 105–111.

IRB Barcelona

El Instituto de Investigación Biomédica (IRB Barcelona) trabaja para conseguir una vida libre de enfermedades. Desarrolla una investigación multidisciplinar de excelencia para curar el cáncer y otras enfermedades vinculadas al envejecimiento. Establece colaboraciones con la industria farmacéutica y los principales hospitales para hacer llegar los resultados de la investigación a la sociedad, a través de la transferencia de tecnología, y realiza diferentes iniciativas de divulgación científica para mantener un diálogo abierto con la ciudadanía. El IRB Barcelona es un centro internacional que acoge alrededor de 400 científicos de más de 30 nacionalidades. Reconocido como Centro de Excelencia Severo Ochoa desde 2011, es un centro CERCA y miembro del Barcelona Institute of Science and Technology (BIST).