Study of the Hippo pathway in medulloblastoma: inhibition of YAP and its relation ...
| Grant number: | 14/10519-6 |
| Support type: | Scholarships in Brazil - Post-Doctorate |
| Effective date (Start): | September 01, 2014 |
| Effective date (End): | December 31, 2019 |
| Field of knowledge: | Biological Sciences - Morphology |
| Principal Investigator: | Oswaldo Keith Okamoto |
| Grantee: | Beatriz de Araujo Cortez |
| Home Institution: | Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated research grant: | 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center, AP.CEPID |
| Associated scholarship(s): | 16/24234-9 - The Hippo pathway, asymmetric cell division and the tolerance to aneuploidy in cancer cells, BE.EP.PD |
Abstract Asymmetric cell division is a striking feature of stem cells. It generates two daughter cells with defined distinct fates, ensuring both stem cell self renewal and differentiation. Abnormalities in this process may affect tissue homeostasis leading to tumor formation, as first observed in Drosophila mutants for genes involved in asymmetric cell division. Failures in asymmetric cell division are also observed in cancer stem cells, or tumor initiating cells. These cells have features of stem and cancer cells and are responsible for tumor initiation and propagation. Signaling pathways regulating typical stem cell properties are often activated in these cells, which also display asymmetric division capability. However, recent studies suggest that cancer stem cells divide mostly through symmetric divisions, which favor cell proliferation and tumor growth. The Hippo pathway has been recently reported as one of the altered signaling pathways in tumors and cancer stem cells. This pathway, originally described as a regulator of tissue growth and size, comprises a well characterized central axis which results in the expression of genes related to cell proliferation, pluripotency and apoptosis. The Hippo pathway has recently been related to the balance between proliferation and differentiation, playing a crucial role in stem cell maintenance and tissue homeostasis. In tumors, Hippo´s effectors are generally overexpressed and confer proliferative capability and undifferentiated phenotype to tumor cells. However, the relation between Hippo pathway and asymmetric division of cancer stem cells has not been characterized yet. Investigating this issue may help understand how cell division is regulated in cancer stem cells, and how modulation of such division pattern may affect tumor aggressiveness. | |