Tampering with ERK1/2 Signals for Cancer Treatment

Grants and Contracts Details

Description

Abstract Cancer development often starts from small alterations in the development of central processes of multicellular organisms and can include an increase in the number of cells, or slight differences in their division processes and migration. Every cell has a system of communication that governs these basic cellular activities and coordinates cell actions, i.e., its ‘cell signaling’ system. Errors during the process of signaling or communications have serious consequences, including tumor formation and metastasis. By understanding cell signaling, we will be able to treat all types of cancer more effectively. Cell signaling is a complex network of interconnected signaling events that are coordinated by critical proteins known as scaffolds. Scaffold proteins bring signaling partners into close proximity and help localize signaling complexes to particular cellular locations. Our long-term goal is to understand the mechanisms by which protein scaffolds orchestrate the regulation of particular signaling pathways in human cells as well as their role in tumor progression. Towards this aim, our work currently focuses on analyzing the critical signaling scaffold, Shoc2. Shoc2 functions as a platform that holds several signaling partners together, thereby allowing for efficient signal transmission. To avoid errors of excessive or insufficient signal transmission, Shoc2 itself and its signaling partners need to be controlled very precisely. We found that Shoc2 assembles intricate protein machinery that in turn fine-tunes signals transmitted via the Shoc2 axis. Using a variety of complementary approaches, we propose to identify and study cellular functions that are regulated by Shoc2-transmitted signals, and in particular the cellular signals critical for tumor progression. Ultimately, we hope to translate this knowledge into new therapeutic strategies for controlling invasive tumor cells. In our work we use an innovative comprehensive approach encompassing genetic, state-of-the-art microscopy, as well as advanced cell-based and biophysical methodologies. Of note, we use zebrafish as a vertebrate model to investigate the physiological effect of Shoc2 gene editing on the early stages of development and cancer growth because they offer distinct advantages for early developmental studies, including their transparency, as well as their external and rapid development. Our studies are expected to produce an ambitious and comprehensive mechanistic understanding of how Shoc2 is involved in determining the specificity of tumor signaling outcomes, and has the potential for high impact by laying the groundwork for future studies on the role of Shoc2 in cancer and contributing to the advancement of novel therapeutic strategies and biomarkers.
StatusActive
Effective start/end date8/1/218/1/23

Funding

  • Markey Cancer Center Foundation: $50,000.00

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