A5043531121- Immune cells in cancer
- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Radiomics and Machine Learning in Medical Imaging
- Cancer Cells and Metastasis
- Colorectal Cancer Treatments and Studies
- RNA modifications and cancer
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Chemokine receptors and signaling
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- Medical Imaging Techniques and Applications
- Ferroptosis and cancer prognosis
- Cancer Research and Treatments
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Wnt/β-catenin signaling in development and cancer
- PI3K/AKT/mTOR signaling in cancer
- Cell death mechanisms and regulation
- RNA Research and Splicing
- Cancer Immunotherapy and Biomarkers
- Digestive system and related health
- Cancer, Hypoxia, and Metabolism
Heidelberg University
2012-2025
German Cancer Research Center
2012-2025
Heidelberg Institute for Stem Cell Technology and Experimental Medicine
2021-2025
DKFZ-ZMBH Alliance
2022-2025
Cancer Research UK Scotland Institute
2015-2024
Cancer Research UK
2019-2024
Deutschen Konsortium für Translationale Krebsforschung
2013-2024
Ludwig-Maximilians-Universität München
2010-2021
University of Glasgow
2016
Ruhr University Bochum
2011
Members of the miR-34 family are induced by tumor suppressor p53 and known to inhibit epithelial-to-mesenchymal transition (EMT) therefore presumably suppress early phases metastasis. Here, we determined that exposure human colorectal cancer (CRC) cells cytokine IL-6 activates oncogenic STAT3 transcription factor, which directly represses MIR34A gene via a conserved STAT3-binding site in first intron. Repression was required for IL-6–induced EMT invasion. Furthermore, identified receptor...
Recently, the inhibition of epithelial-mesenchymal-transition (EMT) by p53 has been described as a new mode tumor suppression which presumably prevents metastasis. Here we report that activation down-regulates EMT-inducing transcription factor SNAIL via induction miR-34a/b/c genes. Suppression caused up-regulation and cells displayed EMT markers related features, enhanced migration invasion. Ectopic miR-34a induced mesenchymal-epithelial-transition (MET) down-regulation SNAIL, was mediated...
The metastatic process of colorectal cancer (CRC) is not fully understood and effective therapies are lacking. We show that activation NOTCH1 signaling in the murine intestinal epithelium leads to highly penetrant metastasis (100% metastasis; with >80% liver metastases) Kras
Abstract Colorectal cancer (CRC) is a heterogenous malignancy underpinned by dysregulation of cellular signaling pathways. Previous literature has implicated aberrant JAK/STAT3 signal transduction in the development and progression solid tumors. In this study we investigate effectiveness inhibiting diverse CRC models, establish which contexts high pathway expression prognostic perform depth analysis underlying phenotypes. investigated use JAK inhibitors for anti-cancer activity cell lines,...
Colorectal cancer (CRC) is stratified into four consensus molecular subtypes (CMS1-4). CMS3 represents the metabolic subtype, but its wiring remains largely undefined. To identify underlying tumorigenesis of CMS3, organoids derived from 16 genetically engineered mouse models are analyzed. Upon in vitro Cre-recombinase activation, transformation established and transcriptional profiling reveals that distinct CMSs (CMS2-4) modeled with different organoids. CMS3-like, signature-positive,...
The basic helix-loop-helix transcription factor AP4/TFAP4/AP-4 is encoded by a c-MYC target gene and displays up-regulation concomitantly with in colorectal cancer (CRC) numerous other tumor types. Here genome-wide characterization of AP4 DNA binding mRNA expression was performed using combination microarray, chromatin immunoprecipitation, next-generation sequencing, bioinformatic analyses. Thereby, hundreds induced repressed genes were identified. Besides many involved the control...
Abstract Purpose: Here, we determined whether epigenetic inactivation of miR-34a and miR-34b/c genes may serve as a prognostic marker for distant metastases in colon cancer. Experimental Design: Using case–control study design 94 primary cancer samples with without liver metastases, CpG methylation frequencies promoters, expression miR-34a, its targets c-Met, Snail, β-catenin their value. Results: was detected 45.1% (n = 42 93) the strongly associated to (P 0.003) lymph nodes 0.006). 91.9%...
A chronic inflammatory microenvironment favors tumor progression through molecular mechanisms that are still incompletely defined. In inflammation-induced skin cancers, IL-1 receptor- or caspase-1–deficient mice, mice specifically deficient for the inflammasome adaptor protein ASC (apoptosis-associated speck-like containing a CARD) in myeloid cells, had reduced incidence, pointing to role signaling and activation development. However, fully were not protected, keratinocytes developed more...
// Helge Siemens 1 , Rene Jackstadt Markus Kaller and Heiko Hermeking 1,2,3 Experimental Molecular Pathology, Institute of Ludwig-Maximilians-University München, D-80337 Munich, Germany 2 German Cancer Consortium (DKTK), D-69120 Heidelberg, 3 Research Center (DKFZ), Correspondence: Hermeking, email: Keywords : p53, miR-34a, miR-34b/c, c-Kit, migration, chemoresistance, stemness Received July 23, 2013 Accepted August 4, Published 6, Abstract The c-Kit receptor tyrosine kinase is commonly...
Abstract The transcription factor AP4 mediates epithelial–mesenchymal transition (EMT) in colorectal cancer but its control this setting is not fully understood. Here, we report the definition of a double-negative feedback loop involving and miR-15a/16-1 that regulates EMT metastatic progression. In cells, was downregulated by DNA damage p53-dependent manner. downregulation p53 mediated indirectly tumor-suppressive microRNAs miR-15a miR-16-1, which targeted 3′ untranslated region (3′-UTR)...
Abstract Pancreatic ductal adenocarcinoma (PDAC) patients have a 5-year survival rate of only 8% largely due to late diagnosis and insufficient therapeutic options. Neutrophils are among the most abundant immune cell type within PDAC tumor microenvironment (TME), associated with poor clinical prognosis. However, despite recent advances in understanding neutrophil biology cancer, therapies targeting tumor-associated neutrophils lacking. Here, we demonstrate, using pre-clinical mouse models...
Abstract Different thresholds of Wnt signalling are thought to drive stem cell maintenance, regeneration, differentiation and cancer. However, the principle that oncogenic could be specifically targeted remains controversial. Here we examine requirement BCL9/9l, constituents Wnt-enhanceosome, for intestinal transformation following loss tumour suppressor APC. Although required Lgr5+ cells Bcl9/9l deletion has no impact upon normal homeostasis. Loss BCL9/9l suppressed many features acute APC...
Abstract Right-sided (proximal) colorectal cancer (CRC) has a poor prognosis and distinct mutational profile, characterized by oncogenic BRAF mutations aberrations in mismatch repair TGFβ signalling. Here, we describe mouse model of right-sided colon driven loss epithelial TGFβ-receptor The proximal colonic tumours that develop this exhibit foetal-like progenitor phenotype ( Ly6a/Sca1 + ) and, importantly, lack expression Lgr5 its associated intestinal stem cell signature. These features are...
Abstract KRAS-mutant colorectal cancers are resistant to therapeutics, presenting a significant problem for ∼40% of cases. Rapalogs, which inhibit mTORC1 and thus protein synthesis, significantly less potent in cancer. Using Kras-mutant mouse models mouse- patient-derived organoids, we demonstrate that KRAS with G12D mutation fundamentally rewires translation increase both bulk mRNA-specific initiation. This occurs via the MNK/eIF4E pathway culminating sustained expression c-MYC. By genetic...
Abstract The molecular basis of disease progression from UV-induced precancerous actinic keratosis (AK) to malignant invasive cutaneous squamous cell carcinoma (cSCC) and potentially lethal metastatic remains unclear. DNA sequencing studies have revealed a massive mutational burden but yet illuminate mechanisms progression. Here we perform RNAseq transcriptomic profiling 110 patient samples representing normal sun-exposed skin, AK, primary cSCC reveal continuum differentiated progenitor-like...
The WNT pathway is a pleiotropic signaling that controls developmental processes, tissue homeostasis, and cancer. commonly mutated in many cancers, leading to widespread research into the role of carcinogenesis. Understanding which cancers are reliant upon activation components paramount advancing therapeutic strategies. In addition, building holistic insights not only tumor cells but also microenvironment vital area may be promising strategy multiple immunologically inert cancers. Novel...
Abstract Evasion of apoptosis is a hallmark cancer, which frequently mediated by upregulation the antiapoptotic BCL-2 family proteins. In colorectal cancer (CRC), previous work has highlighted differential protein dependencies determined stage disease. While intestinal stem cells (ISCs) require for adenoma outgrowth and survival during transformation, ISC-specific MCL1 deletion results in disturbed homeostasis, eventually contributing to tumorigenesis. Colon (CSCs), however, no longer depend...