Rho-ROCK Signaling in Normal Physiology and as a Key Player in Shaping the Tumor Microenvironment

Abstract

The Rho-ROCK signaling network has a range of specialized functions of key biological importance, including control of essential developmental processes such as morphogenesis and physiological processes including homeostasis, immunity, and wound healing. Deregulation of Rho-ROCK signaling actively contributes to multiple pathological conditions, and plays a major role in cancer development and progression. This dynamic network is critical in modulating the intricate communication between tumor cells, surrounding diverse stromal cells and the matrix, shaping the ever-changing microenvironment of aggressive tumors. In this chapter, we overview the complex regulation of the Rho-ROCK signaling axis, its role in health and disease, and analyze progress made with key approaches targeting the Rho-ROCK pathway for therapeutic benefit. Finally, we conclude by outlining likely future trends and key questions in the field of Rho-ROCK research, in particular surrounding Rho-ROCK signaling within the tumor microenvironment.

Keywords: Actomyosin cytoskeleton; Development; Disease; Extracellular matrix; Metastasis; Pancreatic cancer; ROCK inhibitors; Rho-ROCK signaling; Stroma; Targeted therapy; Tumor microenvironment.