title: Esophageal cancer-related gene 4 at the interface of injury, inflammation, infection, and malignancy.
abstract: In humans, esophageal cancer-related gene 4 (ECRG4) is encoded by four exons in the c2orf40 locus of chromosome 2. Translation of ECRG4 messenger ribonucleic acid produces a 148 amino acid-secreted 17 KDa protein that is then processed to 14, ten, eight, six, four, and two KDa peptides, depending on the cell in which the gene is expressed. As hypermethylation at the c2orf40 locus inhibits ECRG4 gene expression in many epithelial cancers, several investigators have speculated that ECRG4 is a candidate tumor suppressor. Indeed, overexpression of ECRG4 inhibits cell proliferation in vitro, but it also has a wide range of effects in vivo beyond its antitumor activity. ECRG4 overexpression affects apoptosis, senescence, cell migration, inflammation, injury, and infection responsiveness. ECRG4 activities also depend on its cellular localization, secretion, and post-translational processing. These cytokine/chemokine-like characteristics argue that ECRG4 is not a traditional candidate tumor suppressor gene, as originally predicted by its downregulation in cancer. We review how insights into the regulation of ECRG4 gene expression, knowledge of its primary structure, and the study of its emerging physiological functions come together to support a much more complex role for ECRG4 at the interface of inflammation, infection, and malignancy.
authors.affiliation: Division of Trauma, Burn, and Acute Critical Care, Department of Surgery, University of California San Diego Health Sciences, San Diego, CA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Baird
authors.affiliation: Division of Trauma, Burn, and Acute Critical Care, Department of Surgery, University of California San Diego Health Sciences, San Diego, CA, USA.
authors.forename: Jisook
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Trauma, Burn, and Acute Critical Care, Department of Surgery, University of California San Diego Health Sciences, San Diego, CA, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Podvin
authors.affiliation: Division of Trauma, Burn, and Acute Critical Care, Department of Surgery, University of California San Diego Health Sciences, San Diego, CA, USA.
authors.forename: Arwa
authors.initials: A
authors.lastname: Kurabi
authors.affiliation: Division of Trauma, Burn, and Acute Critical Care, Department of Surgery, University of California San Diego Health Sciences, San Diego, CA, USA.
authors.forename: Xitong
authors.initials: X
authors.lastname: Dang
authors.affiliation: Division of Trauma, Burn, and Acute Critical Care, Department of Surgery, University of California San Diego Health Sciences, San Diego, CA, USA.
authors.forename: Raul
authors.initials: R
authors.lastname: Coimbra
authors.affiliation: Division of Trauma, Burn, and Acute Critical Care, Department of Surgery, University of California San Diego Health Sciences, San Diego, CA, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Costantini
authors.affiliation: Division of Trauma, Burn, and Acute Critical Care, Department of Surgery, University of California San Diego Health Sciences, San Diego, CA, USA.
authors.forename: Vishal
authors.initials: V
authors.lastname: Bansal
authors.affiliation: Division of Trauma, Burn, and Acute Critical Care, Department of Surgery, University of California San Diego Health Sciences, San Diego, CA, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Eliceiri
keywords: ECRG4; c2orf40; chemokine; cytokine; growth inhibitor; tumor suppressor