Translationa Control In Cancer - Part II

Abstract

Cellular processes such as proliferation and differentiation depend on the correct control of mRNA translation. It is well known that the translation of mRNAs that promote tumor growth is favored by the alteration of signaling pathways that regulate the process of protein synthesis. Thus, translational control in tumors is especially important for regulating gene expression at the level of protein formation. In this project we intend to study different aspects of the translational control and how this control affects tumorigenic processes. In the first part of this project, funded by FAPESP Grant 2014/15550-9, we established an innovative method of studying differentially translated RNAs, which led to the determination of clinically relevant molecular subgroups for tumor types such as glioblastomas.In this second part of the project, we intend to validate the findings of differentially translated RNAs in glioblastomas and extend the study to other tumor types such as breast adenocarcinoma and clear cell renal carcinoma, which also have described alterations in signaling pathways that regulate translation. As a complementary strategy, proteins involved in translational control will also be evaluated in these tumors, such as translation initiation factors (eIFs). In addition, other less well-known modes of translation control will be explored, such as methylation of messenger RNAs. These pathways will be explored in functional models and human samples. These complementary approaches have the potential to unravel mechanisms still poorly understood in tumor biology and to assist both the development of new therapies and the effective application of personalized medicine to patients with selected molecular profiles. (AU)