title: IL10R2 Overexpression Promotes IL22/STAT3 Signaling in Colorectal Carcinogenesis.
abstract: The mucosal immune response in the setting of intestinal inflammation contributes to colorectal cancer. IL10 signaling has a central role in gut homeostasis and is impaired in inflammatory bowel disease (IBD). Out of two IL10 receptor subunits, IL10R1 and IL10R2, the latter is shared among the IL10 family of cytokines and activates STAT signaling. STAT3 is oncogenic in colorectal cancer; however, knowledge about IL10 signaling upstream of STAT3 in colorectal cancer is lacking. Here, expression of IL10 signaling genes was examined in matched pairs from normal and tumor tissue from colorectal cancer patients showing overexpression (mRNA, protein) of IL10R2 and STAT3 but not IL10R1. IL10R2 overexpression was related to microsatellite stability. Transient overexpression of IL10R2 in HT29 cells increased proliferation upon ligand activation (IL10 and IL22). IL22, and not IL10, phosphorylated STAT3 along with increased phosphorylation of AKT and ERK. A significantly higher expression of IL22R1 and IL10R2 was also confirmed in a separate cohort of colorectal cancer samples. IL22 expression was elevated in gut mucosa from patients with IBD and colitis-associated cancer, which also exhibited increased expression of IL22R1 but not its coreceptor IL10R2. Overall, these data indicate that overexpression of IL10R2 and STAT3 contributes to colorectal carcinogenesis in microsatellite-stable tumors through IL22/STAT3 signaling.
authors.affiliation: Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Christian Doppler Laboratory for Molecular Cancer Chemoprevention, Vienna, Austria.
authors.forename: Vineeta
authors.initials: V
authors.lastname: Khare
authors.affiliation: Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Christian Doppler Laboratory for Molecular Cancer Chemoprevention, Vienna, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Paul
authors.affiliation: Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Christian Doppler Laboratory for Molecular Cancer Chemoprevention, Vienna, Austria.
authors.forename: Oliver
authors.initials: O
authors.lastname: Movadat
authors.affiliation: Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Christian Doppler Laboratory for Molecular Cancer Chemoprevention, Vienna, Austria.
authors.forename: Adrian
authors.initials: A
authors.lastname: Frick
authors.affiliation: Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Christian Doppler Laboratory for Molecular Cancer Chemoprevention, Vienna, Austria.
authors.forename: Manuela
authors.initials: M
authors.lastname: Jambrich
authors.affiliation: Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Christian Doppler Laboratory for Molecular Cancer Chemoprevention, Vienna, Austria.
authors.forename: Anita
authors.initials: A
authors.lastname: Krnjic
authors.affiliation: Department of Medicine 1, Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Marian
authors.affiliation: Institute of Clinical Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Wrba
authors.affiliation: Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Christian Doppler Laboratory for Molecular Cancer Chemoprevention, Vienna, Austria. christoph.gasche@meduniwien.ac.at.
authors.forename: Christoph
authors.initials: C
authors.lastname: Gasche
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D063646:Carcinogenesis / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D018928:Immunity, Mucosal; D053710:Interleukin-10 Receptor beta Subunit / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D018123:Receptors, Interleukin / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology
chemical_list: C081846:IL10RB protein, human; D053710:Interleukin-10 Receptor beta Subunit; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C415369:interleukin-22 receptor