A5090451620- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- MicroRNA in disease regulation
- Genetic factors in colorectal cancer
- Cancer Cells and Metastasis
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Cancer Genomics and Diagnostics
- Chromosomal and Genetic Variations
- Epigenetics and DNA Methylation
- Digestive system and related health
- Microtubule and mitosis dynamics
- Circular RNAs in diseases
- DNA Repair Mechanisms
- Plant Molecular Biology Research
- CRISPR and Genetic Engineering
- Cytokine Signaling Pathways and Interactions
- Fibroblast Growth Factor Research
- Cancer-related Molecular Pathways
- thermodynamics and calorimetric analyses
- Signaling Pathways in Disease
- Protist diversity and phylogeny
- PARP inhibition in cancer therapy
- Hippo pathway signaling and YAP/TAZ
- Cancer, Hypoxia, and Metabolism
Ludwig-Maximilians-Universität München
2014-2024
German Cancer Research Center
2015
Heidelberg University
2015
Friedrich Miescher Institute
2014
University of Kassel
2006-2008
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 gene encoding the miR-34a microRNA is a transcriptional target of p53 tumor suppressor protein and subject to epigenetic inactivation in colorectal cancer numerous other types. Here, we combined pulsed SILAC (pSILAC) microarray analyses identify miR-34a-induced changes mRNA expression. pSILAC allowed quantify de novo synthesis 1206 proteins after activation conditional allele cell line. ∼19% detected were differentially regulated, with 113 being down- 115 up-regulated....
// 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...
Epithelial-mesenchymal transition (EMT) plays an important role in tumor invasion and metastasis. A comprehensive, bioinformatics analysis of CCLE TCGA datasets seven types allowed us to identify a novel pan-cancer EMT-associated gene expression signature consisting 16 epithelial 4 mesenchymal state-associated mRNAs. Among the identified cell factors, down-regulation RBM47 (RNA binding motif protein 47) mRNA displayed most significant association with metastasis poor survival multiple...
We determined the effect of p53 activation on de novo protein synthesis using quantitative proteomics (pulsed stable isotope labeling with amino acids in cell culture/pSILAC) colorectal cancer line SW480. This was combined mRNA and noncoding RNA expression analyses by next generation sequencing (RNA-, miR-Seq). Furthermore, genome-wide DNA binding analyzed chromatin-immunoprecipitation (ChIP-Seq). Thereby, we identified differentially regulated proteins (542 up, 569 down), mRNAs (1258 415...
AP4 (TFAP4) encodes a basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factor and is direct target gene of the oncogenic c-MYC. Here, we set out to determine relevance in human colorectal cancer (CRC) cells.A CRISPR/Cas9 approach was employed generate AP4-deficient CRC cell lines with inducible expression Colony formation, β-gal staining, immunofluorescence, comet homologous recombination (HR) assays RNA-Seq analysis were used effects inactivation. qPCR qChIP analyses performed...
Abstract The miR-34a and miR-34b/c encoding genes represent direct targets of the p53 transcription factor, presumably mediate part tumor suppressive effects p53. Here, we sought to determine their functional relevance by inactivating and/or using a CRISPR/Cas9 approach in colorectal cancer (CRC) cell line HCT116. Concomitant deletion resulted significantly reduced suppression proliferation after activation, enhanced migration, invasion EMT, as well sensitivity chemotherapeutics, increased...
Purpose: Colorectal cancers are composed of phenotypically different tumor cell subpopulations within the same core genetic background. Here, we identify high expression TALE transcription factor PBX3 in cells undergoing epithelial-mesenchymal transition (EMT), analyze regulation, and determine clinical associations colorectal cancer.Experimental design: We used transcriptomic situ analyses to cancer biology approaches its regulation function. Clinical were analyzed independent tissue...
Hepatoblastoma (HB) is the most common malignant liver tumor in childhood and it generally has a good prognosis. However, if associated with aggressive metastatic disease, outcome still poor. The molecular mechanisms leading to spread HB patients are unknown. By combining RNA-sequencing genome-wide methylome analysis, we identified transcription factor SP8 growth FGF8 among strongly upregulated genes cases, concomitant robust demethylation of respective promoter regions. Of note, high...
Aurora kinases are highly conserved proteins with important roles in mitosis. Metazoans contain two kinases, A and B, which contribute distinct functions at the spindle poles equatorial region respectively. It is not currently known whether specialized of arose after their duplication animal cells or were already present ancestral kinase. We show that Dictyostelium discoideum contains a single kinase, DdAurora, displays characteristics both B. Like A, DdAurora has an extended N-terminal...
Heterochromatin protein 1 (HP1) is a well-characterized heterochromatin component conserved from fission yeast to humans. We identified three HP1-like genes (hcpA, hcpB, and hcpC) in the Dictyostelium discoideum genome. Two of these (hcpA hcpB) are expressed, proteins colocalized as green fluorescent (GFP) fusion one major cluster at nuclear periphery that was also characterized by histone H3 lysine 9 dimethylation, modification so far not described for Dictyostelium. The data strongly...
Abstract Resistance towards cancer treatment represents a major clinical obstacle, preventing cure of patients. To gain mechanistic insights, we developed model for acquired resistance to chemotherapy by treating mice carrying patient derived xenografts (PDX) acute lymphoblastic leukemia with widely-used cytotoxic drugs 18 consecutive weeks. In two distinct PDX samples, tumors initially responded treatment, until stable disease and eventually tumor re-growth evolved under therapy, at highly...
Abstract The gene encoding the transcription factor TFAP4/AP4 represents a direct target of c-MYC oncoprotein. Here, we deleted Ap4 in Apc Min mice, preclinical model inherited colorectal cancer. deficiency extends their average survival by 110 days and decreases formation intestinal adenomas tumor-derived organoids. effects deletion are presumably due to reduced number functional stem cells (ISCs) amenable adenoma-initiating mutational events. Deletion also colonic increases Paneth cells....
// Markus Kaller 1 , Ursula Götz and Heiko Hermeking 1, 2, 3 Experimental Molecular Pathology, Institute of Ludwig-Maximilians-University Munich, Germany 2 German Cancer Consortium (DKTK), Heidelberg, Research Center (DKFZ), Correspondence to: Hermeking, email: heiko.hermeking@med.uni-muenchen.de Keywords: p53; LINC01021; chemosensitivity; colorectal cancer; tumor suppression Received: September 29, 2017 Accepted: October 02, Published: November 01, ABSTRACT We have previously identified the...
The CSF1 receptor (CSF1R) encoding mRNA represents a direct target of miR-34a.However, the in vivo relevance suppression CSF1R by miR-34a for intestinal tumor mediated p53/miR-34a pathway has remained unknown.Here, Apc Min/+ mice with intestinal-epithelial cell (IEC)-specific deletions Mir34a showed increased formation adenomas and decreased survival, whereas deletion Csf1r adenoma survival.In enhanced proliferation, STAT3 signaling, infiltration fibroblasts, immune cells microbes, stem...
Background: The deregulated expression of the c-MYC oncogene activates p53, which is presumably mediated by ARF/INK4, as well replication-stress-induced DNA damage. Here, we aimed to determine whether c-MYC-inducible AP4 transcription factor plays a role in this context using genetic approach. Methods: We used CRISPR/Cas9 approach generate AP4- and/or p53-deficient derivatives MCF-7 breast cancer cells harboring an ectopic, inducible allele. Cell proliferation, senescence, damage, and...
We have identified expression of the gene encoding transcriptional coactivator FOG-1 (Friend GATA-1; Zfpm1, Zinc finger protein multitype 1) in B lymphocytes. found that is directly or indirectly dependent on cell-specific OBF-1 and it modulated during cell development: observed early but not late stages development. To test vivo role lymphocytes, we developed a novel embryonic stem recombination system. For this, combined homologous with FLP recombinase activity to rapidly generate lines...