title: The dynamics of Rho GTPase signaling and implications for targeting cancer and the tumor microenvironment.
abstract: Numerous large scale genomics studies have demonstrated that cancer is a molecularly heterogeneous disease, characterized by acquired changes in the structure and DNA sequence of tumor genomes. More recently, the role of the equally complex tumor microenvironment in driving the aggressiveness of this disease is increasingly being realized. Tumor cells are surrounded by activated stroma, creating a dynamic environment that promotes cancer development, metastasis and chemoresistance. The Rho family of small GTPases plays an essential role in the regulation of cell shape, cytokinesis, cell adhesion, and cell motility. Importantly, these processes need to be considered in the context of a complex 3-dimensional (3D) environment, with reciprocal feedback and cross-talk taking place between the tumor cells and host environment. Here we discuss the role of molecular networks involving Rho GTPases in cancer, and the therapeutic implications of inhibiting Rho signaling in both cancer cells and the emerging concept of targeting the surrounding stroma.
authors.affiliation: a The Kinghorn Cancer Center; Cancer Division; Garvan Institute of Medical Research ; Sydney , Australia.
authors.forename: Marina
authors.initials: M
authors.lastname: Pajic
authors.forename: David
authors.initials: D
authors.lastname: Herrmann
authors.forename: Claire
authors.initials: C
authors.lastname: Vennin
authors.forename: James Rw
authors.initials: JR
authors.lastname: Conway
authors.forename: Venessa T
authors.initials: VT
authors.lastname: Chin
authors.forename: Anna-Karin E
authors.initials: AK
authors.lastname: Johnsson
authors.forename: Heidi Ce
authors.initials: HC
authors.lastname: Welch
authors.forename: Paul
authors.initials: P
authors.lastname: Timpson
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D015290:Second Messenger Systems; D059016:Tumor Microenvironment; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D020741:rho GTP-Binding Proteins
keywords: ECM; FLIM; FRET; Rho GTPase; Rho inhibitors; cancer stroma; chemoresistance; collagen; intravital imaging