Grant: Operating Grant

The RNA-based control of biological processes has always been overlooked in cancer progression and metastases formation. With this proposal, we will uncover how RNA-binding protein can modulate protein expression in order to influence metastatic cancer cells homing toward specific tissues. Growing evidence reveals that tissue microenvironments secreting specific growth factors greatly influence the implantation of migrating cancer cells at specific sites. Our preliminary work on Sam68 showed that this RNA-binding protein involvement in the regulation of mRNA metabolism is highly modulated by posttranslational modifications resulting from complex signaling pathways whose activation originates from external stimulation, such as the microenvironment. These changes in Sam68 mRNA processing activity can directly affect cell morphology, adhesion and migration. In depth analysis suggest that this was not restricted to Sam68, since altering general mRNA translation can also affect cellular adhesion and migration. These observations clearly indicate that mRNA translation modulation, through the regulation of RNA-binding protein, is an essential process for cancer progression and metastatic cell adhesion and migration. This program examines how RNA-binding proteins activities are modulated by the microenvironment and how this affects cellular adhesion, focal adhesion maturation, changes in cellular morphology and migration. Elucidating how RNA-binding proteins regulates these cellular events is essential since they are mandatory steps for early events in tumor cell dissemination from the primary site to secondary sites to form metastases, the leading cause of cancer-related deaths. Our research will offer novel strategies that could lead to new therapeutic possibilities in order to decrease cancer related mortality due to metastases formation.