Florian Greten

Speaker, Director

Research Focus:

  • Molecular mechanisms in the tumor microenvironment
  • Signaling pathways contributing to metastasis in CRC

Expertise and Technologies for FCI:

  • Preclinical models especially gastrointestinal tumor models
  • 3D-cultures/organoids
  • Clinical translation program Rectal Carcinoma (Link to page – to come)

Core Publications

  • The inflammatory pathogenesis of colorectal cancer
    Schmitt M, Greten FR.
    Here, we review our current understanding of how colon cancer cells interact with their microenvironment, comprised of immune cells, stromal cells and the intestinal microbiome, to suppress or escape immune responses and how inflammatory processes shape the immune pathogenesis of CRC. PubMed
  • Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity During Tumorigenesis
    Paul K Ziegler , Julia Bollrath , Charles K Pallangyo, Takaji Matsutani, Özge Canli, Tiago De Oliveira Michaela A Diamanti, Nina Müller, Jaba Gamrekelashvili, Tracy Putoczki, David Horst, Arun K Mankan, Meryem G Öner Susanna Müller, Josef Müller-Höcker, Thomas Kirchner, Julia Slotta-Huspenina, M Mark Taketo, Thomas Reinheckel , Stefan Dröse , Andrew C Larner, Winfried S Wels, Matthias Ernst, Tim F Greten, Melek C Arkan, Thomas Korn, Dagmar Wirth, Florian R Greten
    Our findings highlight a so-far-unrecognized link between mitochondrial function, lysosomal integrity, and MHC class I presentation in IECs and suggest that therapies triggering mitophagy or inducing LMP in IECs may prove successful in shifting the balance toward anti-tumor immunity in colorectal cancer. PubMed
  • Inflammation and Cancer: Triggers, Mechanisms, and Consequences
    Florian R Greten, Sergei I Grivennikov
    Defining the cornerstone rules of engagement governing molecular and cellular mechanisms of tumor-promoting inflammation will be essential for further development of anti-cancer therapies. PubMed
See more Publications

Research Summary

The notion that chronic inflammatory diseases are associated with an elevated risk of tumorigenesis and Rudolf Virchow’s findings in the late 19th century when he described the high frequency of leucocytes in tumor areas led the basis for genetic studies specifically examining the links between inflammation and cancer. Only during the last decade yet with a steadily increasing pace, clear evidence has been gathered about the underlying molecular mechanisms that could prove the existence of such connection. Thus, by now the link between inflammation and cancer is undisputedly accepted and it has become evident that an inflammatory microenvironment is an essential component of basically all tumors.

The tumor microenvironment is comprised of tumor cells, fibroblasts, endothelial cells as well as cells of the innate and adaptive immune system. These cells communicate and act in an autocrine and paracrine manner on each other, which keeps the cytokine milieu in a finely tuned balance. It is the expression of various immune mediators as well as the abundance of certain cell types in the tumor microenvironment that decides in whether tumor-mediated immunosuppression promoting tumor growth or whether anti-tumor immunity leading to tumor cell elimination prevails.

Our research intends to dissect the cellular and molecular changes in the tumor microenvironment that support gastrointestinal tumor growth. Using conditional knockout technology we functionally examine key signal transduction pathways in various cell types of the tumor microenvironment.
We are using well characterized autochthonous tumor models to

(i) focus on the molecular pathogenesis

(ii) the establishment and further development of imaging modalities to improve diagnostic capacity and

(iii) to evaluate pre-clinical therapeutic studies using novel compounds as well novel combinations of already clinically approved compounds.

Finally, we aim to translate our basic research into clinical applications in close collaboration with our clinical partners at the University Hospital.

Publications

  • Loss of SUV420H2-dependent chromatin compaction drives right-sided colon cancer progression
    PubMed
  • Cancer-associated fibroblasts in inflammation and anti-tumor immunity
    PubMed
  • Colon tumour cell death causes mTOR dependence by paracrine P2X4 stimulation
    PubMed
  • Expansion of T memory stem cells with superior anti-tumor immunity by Urolithin A-induced mitophagy
    PubMed
  • Olfactomedin 4 associates with expression of differentiation markers but not with properties of cancer stemness, EMT nor metastatic spread in colorectal cancer
    PubMed
  • Image-guided radiotherapy in an orthotopic mouse model of rectal cancer
    PubMed
  • Inflammation: the incubator of the tumor microenvironment
    PubMed
  • ACO/ARO/AIO-21 - Capecitabine-based chemoradiotherapy in combination with the IL-1 receptor antagonist anakinra for rectal cancer Patients: A phase I trial of the German rectal cancer study group
    PubMed
  • IKKα Promotes Intestinal Tumorigenesis by Limiting Recruitment of M1-like Polarized Myeloid Cells
    PubMed
  • Inflammatory fibroblasts mediate resistance to neoadjuvant therapy in rectal cancer
    PubMed
  • Disruption of Prostaglandin E2 Signaling in Cancer-Associated Fibroblasts Limits Mammary Carcinoma Growth but Promotes Metastasis
    PubMed
  • KMT9 Controls Stemness and Growth of Colorectal Cancer
    PubMed
  • The inflammatory pathogenesis of colorectal cancer
    PubMed
  • Immune cell - produced ROS and their impact on tumor growth and metastasis
    PubMed
  • Inducible mouse models of colon cancer for the analysis of sporadic and inflammation-driven tumor progression and lymph node metastasis
    PubMed
  • A Wnt-Induced Phenotypic Switch in Cancer-Associated Fibroblasts Inhibits EMT in Colorectal Cancer
    PubMed
  • Fructose stimulated de novo lipogenesis is promoted by inflammation
    PubMed
  • AKT-dependent NOTCH3 activation drives tumor progression in a model of mesenchymal colorectal cancer
    PubMed
  • S1PR4 ablation reduces tumor growth and improves chemotherapy via CD8+ T cell expansion
    PubMed
  • A framework for advancing our understanding of cancer-associated fibroblasts
    PubMed
  • STAT3 activation through IL-6/IL-11 in cancer-associated fibroblasts promotes colorectal tumour development and correlates with poor prognosis
    PubMed
  • Inflammation and Cancer: Triggers, Mechanisms, and Consequences
    PubMed
  • Modulating inflammation for cancer therapy
    PubMed
  • Loss of Stat6 affects chromatin condensation in intestinal epithelial cells causing diverse outcome in murine models of inflammation-associated and sporadic colon carcinogenesis
    PubMed
  • Fungi Enter the Stage of Colon Carcinogenesis
    PubMed
  • Therapeutic Ablation of Gain-of-Function Mutant p53 in Colorectal Cancer Inhibits Stat3-Mediated Tumor Growth and Invasion
    PubMed
  • Chronic intestinal inflammation in mice expressing viral Flip in epithelial cells
    PubMed
  • Circulating hypoxia marker carbonic anhydrase IX (CA9) in patients with hepatocellular carcinoma and patients with cirrhosis
    PubMed
  • Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis
    PubMed
  • NoxO1 Controls Proliferation of Colon Epithelial Cells
    PubMed
  • Canonical NF-κB signaling in myeloid cells promotes lung metastasis in a mouse breast cancer model
    PubMed
  • Polyol Pathway Links Glucose Metabolism to the Aggressiveness of Cancer Cells
    PubMed
  • Myeloid Cell-Derived Reactive Oxygen Species Induce Epithelial Mutagenesis
    PubMed
  • Cell plasticity in epithelial homeostasis and tumorigenesis
    PubMed
  • TGFβ pathway limits dedifferentiation following WNT and MAPK pathway activation to suppress intestinal tumourigenesis
    PubMed
  • Card9-dependent IL-1β regulates IL-22 production from group 3 innate lymphoid cells and promotes colitis-associated cancer
    PubMed
  • Linear ubiquitination of cytosolic Salmonella Typhimurium activates NF-κB and restricts bacterial proliferation
    PubMed
  • EGFR in Tumor-Associated Myeloid Cells Promotes Development of Colorectal Cancer in Mice and Associates With Outcomes of Patients
    PubMed
  • Cancer: Tumour stem-cell surprises
    PubMed
  • Mesenchymal Cells in Colon Cancer
    PubMed
  • IKKα controls ATG16L1 degradation to prevent ER stress during inflammation
    PubMed
  • The Irony of Tumor-Induced Inflammation
    PubMed
  • Inflammation and cancer: tissue regeneration gone awry
    PubMed
  • Pseudo-HE images derived from CARS/TPEF/SHG multimodal imaging in combination with Raman-spectroscopy as a pathological screening tool
    PubMed
  • High levels of the soluble programmed death-ligand (sPD-L1) identify hepatocellular carcinoma patients with a poor prognosis
    PubMed
  • The Prosurvival IKK-Related Kinase IKKε Integrates LPS and IL17A Signaling Cascades to Promote Wnt-Dependent Tumor Development in the Intestine
    PubMed
  • Bcl-2 is a critical mediator of intestinal transformation
    PubMed
  • Lifting the Mist on Gastric Stem Cells
    PubMed
  • Systematic evaluation of the biological variance within the Raman based colorectal tissue diagnostics
    PubMed
  • IKKβ acts as a tumor suppressor in cancer-associated fibroblasts during intestinal tumorigenesis
    PubMed
  • Glutathione peroxidase 4 prevents necroptosis in mouse erythroid precursors
    PubMed
  • TAK1 and IKK2, novel mediators of SCF-induced signaling and potential targets for c-Kit-driven diseases
    PubMed
  • Subthreshold IKK activation modulates the effector functions of primary mast cells and allows specific targeting of transformed mast cells
    PubMed
  • Corrigendum. IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis
    PubMed
  • Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche
    PubMed
  • Selective in vivo imaging of syngeneic, spontaneous, and xenograft tumors using a novel tumor cell-specific hsp70 peptide-based probe
    PubMed
  • High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity
    PubMed
  • YAP1 takes over when oncogenic K-Ras slumbers
    PubMed
  • The architect who never sleeps: tumor-induced plasticity
    PubMed
  • IKKα promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells
    PubMed
  • IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis
    PubMed
  • Cell Autonomous and Non-Autonomous Functions of IKKβ and NF-κB during the Pathogenesis of Gastrointestinal Tumors
    PubMed
  • Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically
    PubMed
  • Concurrent video-rate color and near-infrared fluorescence laparoscopy
    PubMed
  • Trp53 deficiency protects against acute intestinal inflammation
    PubMed
  • ROS production and NF-κB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation
    PubMed
  • The gastrointestinal tumor microenvironment
    PubMed
  • Tumor fibroblast-derived epiregulin promotes growth of colitis-associated neoplasms through ERK
    PubMed
  • Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties
    PubMed
  • Loss of p53 in enterocytes generates an inflammatory microenvironment enabling invasion and lymph node metastasis of carcinogen-induced colorectal tumors
    PubMed
  • Inhibiting signal transducer and activator of transcription 3: rationality and rationale design of inhibitors
    PubMed
  • TAK1: Another mesh in the NF-κB - JNK controlled network causing hepatocellular carcinoma
    PubMed
  • TNF-alpha-dependent loss of IKKbeta-deficient myeloid progenitors triggers a cytokine loop culminating in granulocytosis
    PubMed
  • Up and downregulation of p16(Ink4a) expression in BRAF-mutated polyps/adenomas indicates a senescence barrier in the serrated route to colon cancer
    PubMed
  • IkappaBbeta is an essential co-activator for LPS-induced IL-1beta transcription in vivo
    PubMed
  • Peering into the aftermath: JAKi rips STAT3 in cancer
    PubMed
  • IKK- and NF-κB-mediated functions in carcinogenesis
    PubMed
  • Ink4a/Arf and oncogene-induced senescence prevent tumor progression during alternative colorectal tumorigenesis
    PubMed
  • Immunity, inflammation, and cancer
    PubMed
  • IKK/NF-kappaB and STAT3 pathways: central signalling hubs in inflammation-mediated tumour promotion and metastasis
    PubMed
  • Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia
    PubMed
  • Inflammation and mitochondrial fatty acid beta-oxidation link obesity to early tumor promotion
    PubMed
  • gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis
    PubMed
  • Opposing functions of IKKbeta during acute and chronic intestinal inflammation
    PubMed
  • NF-kappaB is a negative regulator of IL-1beta secretion as revealed by genetic and pharmacological inhibition of IKKbeta
    PubMed
  • Epithelial-cell-intrinsic IKK-beta expression regulates intestinal immune homeostasis
    PubMed
  • IKKalpha controls p52/RelB at the skp2 gene promoter to regulate G1- to S-phase progression
    PubMed
  • Genetically induced pancreatic adenocarcinoma is highly immunogenic and causes spontaneous tumor-specific immune responses
    PubMed
  • NF-kappaB: linking inflammation and immunity to cancer development and progression
    PubMed
  • Signaling pathways and genes that inhibit pathogen-induced macrophage apoptosis--CREB and NF-kappaB as key regulators
    PubMed
  • IKK-beta links inflammation to obesity-induced insulin resistance
    PubMed
  • Regulation of cyclin D1 expression by autocrine IGF-I in human BON neuroendocrine tumour cells
    PubMed
  • IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer
    PubMed
  • The IKK/NF-kappaB activation pathway-a target for prevention and treatment of cancer
    PubMed
  • IkappaB-kinasebeta-dependent NF-kappaB activation provides radioprotection to the intestinal epithelium
    PubMed
  • Murine pancreatic tumor cell line TD2 bears the characteristic pattern of genetic changes with two independently amplified gene loci
    PubMed
  • Pattern of secondary genomic changes in pancreatic tumors of Tgf alpha/Trp53+/- transgenic mice
    PubMed
  • The two faces of IKK and NF-kappaB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion
    PubMed
  • Stat3 and NF-kappaB activation prevents apoptosis in pancreatic carcinogenesis
    PubMed
  • Cyclosporine inhibits growth through the activating transcription factor/cAMP-responsive element-binding protein binding site in the cyclin D1 promoter
    PubMed