title: Gastrin-releasing peptide signaling alters colon cancer invasiveness via heterochromatin protein 1Hsβ.
abstract: Epithelial cells lining the adult colon do not normally express gastrin-releasing peptide (GRP) or its receptor (GRPR). In contrast, GRP/GRPR can be aberrantly expressed in colon cancer where they are associated with improved patient survival rates. However, the mechanism of action whereby these proteins mediate their beneficial effects is not known. Heterochromatin protein 1 is an epigenetic modifier of gene transcription for which three different isoforms exist in humans: HP1(Hsα), HP1(Hsβ), and HP1(Hsγ). In breast cancer and melanoma, respectively, HP1(Hsα) and HP1(Hsβ) have been shown to modulate the aggressiveness of tumor cells in vivo. In contrast, the role of HP1 in colon cancer has not been elucidated, and a mechanism of regulating the expression of any HP1 isoform in any context has not yet been identified. In this article we demonstrate that abrogating GRP/GRPR signaling specifically down-regulates HP1(Hsβ) expression and that inhibiting GRPR signaling, or ablating HP1(Hsβ) expression, increases colon cancer cell invasiveness in vitro. These findings identify for the first time a signaling pathway regulating heterochromatin protein expression and suggest a mechanism whereby aberrantly expressed GRPR might alter the outcome of patients with colorectal cancer.
authors.affiliation: Departments of Medicine and Biological Sciences, UIC Cancer Center, University of Illinois at Chicago, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Tell
authors.forename: Claudio A
authors.initials: CA
authors.lastname: Rivera
authors.forename: Jillian
authors.initials: J
authors.lastname: Eskra
authors.forename: Lauren N
authors.initials: LN
authors.lastname: Taglia
authors.forename: Adam
authors.initials: A
authors.lastname: Blunier
authors.forename: Q Tian
authors.initials: QT
authors.lastname: Wang
authors.forename: Richard V
authors.initials: RV
authors.lastname: Benya
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D019886:Gastrin-Releasing Peptide / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000378:metabolism; D018004:Receptors, Bombesin / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D034741:RNA, Small Interfering; D018004:Receptors, Bombesin; D000090266:Chromobox Protein Homolog 5; D019886:Gastrin-Releasing Peptide; D003094:Collagen