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Study on the Regulation and Function of the RSK Family in Glioblastomas

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)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
HAJJ, GLAUCIA N. M.; DA SILVA, FERNANDA F.; DE BELLIS, BARBARA; LUPINACCI, FERNANDA C. S.; BELLATO, HERMANO M.; CRUZ, JUVANIER R.; SEGUNDO, CLAUDIONOR N. C.; FAQUINI, V, IGOR; TORRES, LEURIDAN C.; SANEMATSU, I, PAULO; et al. Aberrant expression of RSK1 characterizes high-grade gliomas with immune infiltration. MOLECULAR ONCOLOGY, v. 14, n. 1, p. 159-179, . (15/15451-3, 18/17796-6)
MACHADO, LUIS EDUARDO; ALVARENGA, ARTHUR WILLIAM; DA SILVA, FERNANDA FERREIRA; ROFFE, MARTIN; BEGNAMI, MARIA DIRLEI; BLEGGI TORRES, LUIS FERNANDO; DA CUNHA, ISABELA WERNECK; MARTINS, VILMA REGINA; MAROSO HAJJ, GLAUCIA NOELI. Overexpression of mTOR and p(240-244)S6 in IDH1 Wild-Type Human Glioblastomas Is Predictive of Low Survival. JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, v. 66, n. 6, p. 403-414, . (14/15550-9, 15/15451-3)
LIANG, SHUO; BELLATO, HERMANO MARTINS; LORENT, JULIE; LUPINACCI, FERNANDA C. S.; OERTLIN, CHRISTIAN; VAN HOEF, VINCENT; ANDRADE, VICTOR P.; ROFFE, MARTIN; MASVIDAL, LAIA; HAJJ, GLAUCIA N. M.; et al. Polysome-profiling in small tissue samples. Nucleic Acids Research, v. 46, n. 1, . (14/15550-9, 14/04513-5, 15/15451-3, 13/03315-2)
SULLA LUPINACCI, FERNANDA CRISTINA; KUASNE, HELLEN; ROFFE, MARTIN; VASSALAKIS, JULIA AVIAN; DA SILVA, FERNANDA FERREIRA; SANTOS, TIAGO GOSS; ANDRADE, VICTOR PIANA; SANEMATSU, PAULO; MARTINS, VILMA REGINA; ROGATTO, SILVIA REGINA; et al. Polysome Profiling of a Human Glioblastoma Reveals Intratumoral Heterogeneity. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 9, . (15/15451-3, 18/17796-6)
MAROSO HAJJ, GLAUCIA NOELI; CORDEIRO NUNES, PAULA BORZINO; ROFFE, MARTIN. Genome-wide translation patterns in gliomas: An integrative view. CELLULAR SIGNALLING, v. 79, . (18/17796-6, 15/15451-3)

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