MSU Technologies

Inhibitors of Rho/MRTF/SRF Gene Transcription

Introduction

Cancer metastasis is a significant medical problem in the United States, where it is estimated that >500,000 cancer-related deaths in 2003 were as a result of metastatic tumors rather than effects of the primary tumor (approximately 90% of cancer deaths). Cancer metastasis is a result of malfunction in several tightly regulated cellular processes that control cell movement from a primary site to a secondary site. These cellular processes include cell survival, adhesion, migration, proteolysis as it pertains to extracellular matrix remodeling, immune escape, angiogenesis and lymphangiogenesis, and target ‘homing.’ Most existing treatments of cancers have focused on killing tumor cells. The problem with such chemotherapeutic intervention is that it leads to substantial toxicity. Since spread, or metastasis, of cancers is the primary way in which cancer kills people, it would be desirable to find agents that inhibit or prevent signals that trigger metastasis.

Description of Technology

Michigan State University has developed compositions and methods for the treatment of disorders that involve rho-signaling. The present invention shows that co-transfection of a cell line with two activators of the rho-signaling pathway (LARG and G13) allowed the production of a cell line that facilitated the identification of inhibitors of the rho-signaling pathway. The inhibitors specifically identified herein inhibited rho-mediated gene transcription, SRF-stimulated gene transcription and inhibited and key cancer cell functions such as LPA-stimulated DNA synthesis, cell proliferation, and matrix invasion. As such, these inhibitors can be used as therapeutic agents for any disorder that is mediated through LPA-stimulated DNA synthesis or rho-mediated gene transcription. MSUT reference TEC2015-0023

Key Benefits