| Grant number: | 15/15451-3 |
| Support Opportunities: | Regular Research Grants |
| Start date: | February 01, 2016 |
| End date: | January 31, 2019 |
| Field of knowledge: | Health Sciences - Medicine |
| Principal Investigator: | Martín Roffé |
| Grantee: | Martín Roffé |
| Host Institution: | A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil |
| Associated researchers: | Fabio Albuquerque Marchi ; Glaucia Noeli Maroso Hajj ; Maria Dirlei Ferreira de Souza Begnami ; Silvia Regina Rogatto ; Vilma Regina Martins |
| Associated research grant(s): | 17/50150-0 - Characterization o the RSK-independent mechanisms of BI-D1870 that potentiate the activity of therapeutic oncolytic viruses in glioblastoma cells, AP.R SPRINT |
Abstract
The RSKs (RSK1-4) are a family of kinases directly regulated by the Ras-ERK1/2 pathway. The RSKs have been involved in the control of different functions, such as proliferation and the control of transcription and mRNA translation, in several types of tumors. However, we previously described that two widely-used RSK inhibitors (SL0101 and BI-D1870) are nonspecific, and thus, functions previously ascribed to RSKs should be reassessed. Remarkably, nothing is known about RSK functions in glioblastoma (GB). The GB is the most frequent tumor of the brain and it is highly lethal. The survival time is less than two years with the available treatments. In this manner, the development of more effective therapies depends on a better understanding of the signaling pathways altered in GB. Our preliminary results suggested that the expression of RSKs is highly heterogeneous in cases of GB and cell lines. We also observed an association between the expression of the proteins RSK1 and PTEN, which is especially relevant, since alterations of PTEN are very frequent in GBs. In this project, we will analyze the regulation of several processes in GB (proliferation, invasion, etc.) by RSKs. We will focus on the regulation of mRNA translation by RSKs, since this issue is a matter of debate in the literature. Based on preliminary observations of the relationship between RSK and PTEN, we will try to define the effects of the RSKs in the induction of senescence promoted by PTEN-loss. We thus expect to increase the knowledge about the molecular mechanisms regulating the biology of GBs, and set the base for the development of new therapeutic approaches (AU)
| Articles published in Agência FAPESP Newsletter about the research grant: |
| More itemsLess items |
| TITULO |
| Articles published in other media outlets ( ): |
| More itemsLess items |
| VEICULO: TITULO (DATA) |
| VEICULO: TITULO (DATA) |