title: Proteinase activated-receptors-associated signaling in the control of gastric cancer.
abstract: Gastric cancer (GC) is the fourth most common cancer in the world and the second cause of cancer-related death. Gastric carcinogenesis is a multifactorial process, in which environmental and genetic factors interact to activate multiple intracellular signals thus leading to uncontrolled growth and survival of GC cells. One such a pathway is regulated by proteinase activated-receptors (PARs), seven transmembrane-spanning domain G protein-coupled receptors, which comprise four receptors (i.e., PAR-1, PAR-2, PAR-3, and PAR-4) activated by various proteases. Both PAR-1 and PAR-2 are over-expressed on GC cells and their activation triggers and/or amplifies intracellular pathways, which sustain gastric carcinogenesis. There is also evidence that expression of either PAR-1 or PAR-2 correlates with depth of wall invasion and metastatic dissemination and inversely with the overall survival of patients. Consistently, data emerging from experimental models of GC suggest that both these receptors can be important targets for therapeutic interventions in GC patients. In contrast, PAR-4 levels are down-regulated in GC and correlate inversely with the aggressiveness of GC, thus suggesting a negative role of this receptor in the control of GC. In this article we review the available data on the expression and role of PARs in GC and discuss whether manipulation of PAR-driven signals may be useful for interfering with GC cell behavior.
authors.affiliation: Silvia Sedda, Irene Marafini, Roberta Caruso, Francesco Pallone, Giovanni Monteleone, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, 00133 Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sedda
authors.affiliation: Silvia Sedda, Irene Marafini, Roberta Caruso, Francesco Pallone, Giovanni Monteleone, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, 00133 Rome, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Marafini
authors.affiliation: Silvia Sedda, Irene Marafini, Roberta Caruso, Francesco Pallone, Giovanni Monteleone, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, 00133 Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Caruso
authors.affiliation: Silvia Sedda, Irene Marafini, Roberta Caruso, Francesco Pallone, Giovanni Monteleone, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, 00133 Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pallone
authors.affiliation: Silvia Sedda, Irene Marafini, Roberta Caruso, Francesco Pallone, Giovanni Monteleone, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, 00133 Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Monteleone
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D044462:Receptors, Proteinase-Activated / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D044462:Receptors, Proteinase-Activated
keywords: Gastric cancer; Helicobacter pylori; Infection; Proteinase activated-receptors