Functional analysis of IL-17RA signaling in colorectal carcinogenesis

Abstract:

Using whole body knockouts as well as conditional Il17ra-mutants, we aim at defining the function of IL-17RA signaling during colorectal cancer (CRC) invasion and metastasis in a novel murine autochthonous model of CRC that depends on loss of the tumor suppressor p53. A particular focus will be placed on the changes in the cellular composition of the microenvironment of Il17ra-deficient tumors, the effects on intestinal barrier function and the composition of the intestinal microbiome as well as the effects of IL-17 on EMT and angiogenesis.

Principal investigator:

Prof. Dr. med. Florian R. Greten
Georg-Speyer-Haus
Institut für Tumorbiologie und experimentelle Therapie
Paul-Ehrlich-Straße 42-44, 60596 Frankfurt/Main
Phone: +49 (0)69 63395-232
E-mail: greten@gsh.uni-frankfurt.de
Web: http://www.georg-speyer-haus.de/forschung/forschungsgruppen/greten/forschung.html

Postdoc:

Dr. Charles Pallangyo

 

Project-related publications:

Pallangyo CK, Ziegler PK, Greten FR (2015). IKKbeta acts as a tumor suppressor in cancer-associated fibroblasts during intestinal tumorigenesis. J Exp Med 212: 2253-2266

Schwitalla S, Ziegler PK, Horst D, Becker V, Kerle I, Begus-Nahrmann Y, Lechel A, Rudolph KL, Langer R, Slotta-Huspenina J, Bader FG, Prazeres da Costa O, Neurath MF, Meining A, Kirchner T, Greten FR (2013) Loss of p53 in Enterocytes Generates an Inflammatory Microenvironment Enabling Invasion and Lymph Node Metastasis of Carcinogen-Induced Colorectal Tumors. Cancer Cell 23: 93-106

Grivennikov SI, Greten FR, Karin M (2010). Immunity, inflammation, and cancer. Cell 140: 883-899

Bollrath J, Phesse TJ, von Burstin VA, Putoczki T, Bennecke M, Bateman T, Nebelsiek T, Lundgren-May T, Canli O, Schwitalla S, Matthews V, Schmid RM, Kirchner T, Arkan MC, Ernst M, Greten FR (2009) gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 15: 91-102

Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF, Karin M (2004) IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118: 285-296