Project A7

Regulation and function of the S100A8/S100A9 protein complex in inflammation-associated liver carcinogenesis

Principal Investigators: Prof. Dr. Peter Angel, PD. Dr. Jochen Heß


Short Summary

Enhanced levels of the pro-inflammatory proteins S100A8 and S100A9 are hallmarks of chronic inflammation and epithelial cancer. Recently, we found increased S100A8/A9 expression during malignant progression of mouse and human liver carcinogenesis and provided experimental evidence that they activate ROS-dependent signaling and protect hepatocellular tumor cells from apoptosis. The goal of our proposed project is the establishment of pre-clinical mouse model systems for translational cancer research and the development of strategies to target components of S100A8/A9-induced signaling pathways and genetic networks as novel therapeutic option.


List of relevant publications

1.   Busch H, Camacho-Trullio D, Rogon Z, Breuhahn K, Angel P, Eils R, Szabowski A (2008) Gene network dynamics controlling keratinocyte migration. Mol Syst Biol 4:199.

2.   Durchdewald M, Guinea-Viniegra J, Haag D, Riehl A, Lichter P, Hahn M, Wagner EF, Angel P, Hess J (2008) Podoplanin is a novel fos target gene in skin carcinogenesis. Cancer Res 68(17):6877-83.

3.   Gebhardt C, Riehl A, Durchdewald M, Nemeth J, Furstenberger G, Muller-Decker K, Enk A, Arnold B, Bierhaus A, Nawroth PP, Hess J, Angel P (2008) RAGE signaling sustains inflammation and promotes tumor development. J Exp Med 205:275-85.

4.   Haase D, Meister M, Muley T, Hess J, Teurich S, Schnabel P, Hartenstein B, Angel P (2007) FRMD3, a novel putative tumour suppressor in NSCLC. Oncogene 26:4464-8.

5.   Schmidt D, Textor B, Pein OT, Licht AH, Andrecht S, Sator-Schmitt M, Fusenig NE, Angel P, Schorpp-Kistner M (2007) Critical role for NF-kappaB-induced JunB in VEGF regulation and tumor angiogenesis. Embo J 26:710-9.

6.   Klucky B, Mueller R, Vogt I, Teurich S, Hartenstein B, Breuhahn K, Flechtenmacher C, Angel P, Hess J (2007) Kallikrein 6 induces e-cadherin shedding and promotes cell proliferation, migration, and invasion. Cancer Res 67:8198-206.

7.   Bourcier C, Jacquel A, Hess J, Peyrottes I, Angel P, Hofman P, Auberger P, Pouyssegur J, Pages G (2006) p44 mitogen-activated protein kinase (extracellular signal-regulated kinase 1)-dependent signaling contributes to epithelial skin carcinogenesis. Cancer Res 66:2700-7.

8.   Hummerich L, Muller R, Hess J, Kokocinski F, Hahn M, Furstenberger G, Mauch C, Lichter P, Angel P (2006) Identification of novel tumour-associated genes differentially expressed in the process of squamous cell cancer development. Oncogene 25:111-21.

9.   Licht AH, Pein OT, Florin L, Hartenstein B, Reuter H, Arnold B, Lichter P, Angel P, Schorpp-Kistner M (2006) JunB is required for endothelial cell morphogenesis by regulating core-binding factor beta. J Cell Biol 175:981-91.

10.  Gebhardt C, Nemeth J, Angel P, Hess J (2006) S100A8 and S100A9 in inflammation and cancer. Biochem Pharmacol 72:1622-31.

11.  Rhiemeier V, Breitenbach U, Richter KH, Gebhardt C, Vogt I, Hartenstein B, Furstenberger G, Mauch C, Hess J, Angel P (2006) A novel aspartic proteinase-like gene expressed in stratified epithelia and squamous cell carcinoma of the skin. Am J Pathol 168:1354-64.

12.  Zenz R, Eferl R, Kenner L, Florin L, Hummerich L, Mehic D, Scheuch H, Angel P, Tschachler E, Wagner EF (2005) Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins. Nature 437:369-75.

13.  Hermani A, Hess J, De Servi B, Medunjanin S, Grobholz R, Trojan L, Angel P, Mayer D (2005) Calcium-binding proteins S100A8 and S100A9 as novel diagnostic markers in human prostate cancer. Clin Cancer Res;11:5146-52.

14.  Gebhardt C, Breitenbach U, Richter KH, Furstenberger G, Mauch C, Angel P, Hess J (2005) c-Fos-Dependent Induction of the Small Ras-Related GTPase Rab11a in Skin Carcinogenesis. Am J Pathol 167:243-53.

15.  Florin L, Hummerich L, Dittrich BT, Kokocinski F, Wrobel G, Gack S, Schorpp-Kistner M, Werner S, Hahn M, Lichter P, Szabowski A, Angel P (2004) Identification of novel AP-1 target genes in fibroblasts regulated during cutaneous wound healing. Oncogene 23:7005-17.

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