A5041117801- TGF-β signaling in diseases
- Cancer-related Molecular Pathways
- Bone Metabolism and Diseases
- Cancer, Hypoxia, and Metabolism
- Protein Kinase Regulation and GTPase Signaling
- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- Pulmonary Hypertension Research and Treatments
- Nitric Oxide and Endothelin Effects
- Growth Hormone and Insulin-like Growth Factors
- NF-κB Signaling Pathways
- Mechanisms of cancer metastasis
- High Altitude and Hypoxia
- Mitochondrial Function and Pathology
- Vascular Anomalies and Treatments
- Fibroblast Growth Factor Research
- Proteoglycans and glycosaminoglycans research
- French Historical and Cultural Studies
- Data-Driven Disease Surveillance
- Pancreatic and Hepatic Oncology Research
- Ubiquitin and proteasome pathways
- Cancer Cells and Metastasis
- Connective Tissue Growth Factor Research
- Cancer Treatment and Pharmacology
Uppsala University
2011-2025
Science for Life Laboratory
2012-2024
Ludwig Cancer Research
2012-2019
Crete University Press
2016
University of Crete
2005-2016
Ludwig Cancer Research
2011-2012
Lankenau Institute for Medical Research
2012
Institute of Cancer Research
2012
Imperial College London
2012
Foundation for Research and Technology Hellas
2008-2009
Dysregulated bone morphogenetic protein (BMP) signaling in endothelial cells (ECs) and pulmonary arterial smooth muscle (PASMCs) are implicated human genetic disorders. Here, we generated genome-wide maps of Smad1/5 binding sites ECs PASMCs. preferentially bound to the region outside promoter known genes, was associated with target gene upregulation. Cell-selective patterns appear be determined mostly by cell-specific differences baseline chromatin accessibility patterns. We identified, for...
It is well established that transforming growth factor-β (TGFβ) switches its function from being a tumor suppressor to promoter during the course of tumorigenesis, which involves both cell-intrinsic and environment-mediated mechanisms. We are interested in breast cancer cells, SMAD mutations rare interactions between other transcription factors define pro-oncogenic events. Here, we have performed chromatin immunoprecipitation (ChIP)-sequencing analyses indicate genome-wide landscape SMAD2/3...
Abstract Activator protein (AP)-1 transcription factors are essential elements of the pro-oncogenic functions transforming growth factor-β (TGFβ)-SMAD signaling. Here we show that in multiple HER2+ and/or EGFR+ breast cancer cell lines these AP-1-dependent tumorigenic properties TGFβ critically rely on epidermal factor receptor (EGFR) activation and expression ΔN isoform transcriptional regulator p63. EGFR ΔNp63 enabled potentiated a subset TGFβ-inducible invasion/migration-associated genes,...
Rationale: RhoA and Rho kinase contribute to pulmonary vasoconstriction vascular remodeling in hypertension. RhoB, a protein homologous activated by hypoxia, regulates neoplastic growth but its role the regulation of function is not known. Objective: To determine RhoB endothelial smooth muscle cell responses hypoxia chronic hypoxia-induced Methods Results: Hypoxia increased expression activity human artery cells, coincidental with activation RhoA. or adenoviral overexpression constitutively...
ABSTRACT Hyaluronan, p53, and transforming growth factor‐β1 (TGF‐β1) play important roles in skin function. They are involved keratinocyte growth, migration, differentiation, although the way they interact is not well understood. Analysis of p63 genome‐wide chromatin immunoprecipitation sequencing (ChIP‐seq) revealed that ΔNp63, a paralogue binds to genomic loci HAS2 HAS3 , encoding hyaluronan synthases, human‐immortalized HaCaT cells which express mutant p53. Additionally, ΔNp63 binding...
In previous studies, we have demonstrated that RhoA/B-dependent signaling regulates TGFbeta-induced rapid actin reorganization in Swiss 3T3 fibroblasts. Here report TGFbeta long-term remodeling by increasing the steady-state mRNA levels of RhoB gene mouse fibroblasts and human hepatoma HepG2 cells. We show this regulation is specific for facilitated enhanced activity promoter. Adenovirus-mediated transfer Smad2 Smad3 induced transcription endogenous but not RhoA gene. Interestingly, JEG-3...
The p53 family of transcription factors includes p63, which is a master regulator gene expression in epithelial cells. Determining whether p63 tumor-suppressive or tumorigenic complicated by isoform-specific and cellular context-dependent protein associations, as well antagonism from mutant p53. ΔNp63 an amino-terminal-truncated isoform, that is, the predominant isoform expressed cancer cells origin. In HaCaT keratinocytes, have ΔNp63, we found antagonized transcriptional activity but...
In the present study, we have investigated mechanisms of transcriptional co-operation between proteins that belong to tumour suppressor p53 and Sp (specificity protein) families transcription factors. Such may play an important role in regulation genes containing binding sites for both classes factors their promoters. Two these were analysed study: cyclin-dependent kinase inhibitor p21Cip1 gene PUMA (p53-up-regulated mediator apoptosis) gene. We found Sp1 Sp3, but not Sp2, co-operate...
The purpose of the present study was to investigate mechanism transcriptional induction small GTPase RhoB gene by transforming growth factor β (TGFß) signaling pathway and role this regulation in TGFß-induced cell migration. To achieve our goals, we utilized a combination siRNAmediated silencing, adenovirus-mediated transfer receptor MAPK inhibition, transactivation assays, DNA-protein interaction assays human HaCaT keratinocytes. We found that is direct target TGFß. show TGFß activates an...
BMP signaling induces a transcription factor that may block pulmonary arterial hypertension from developing.
Transforming growth factor β (TGFβ) regulates many physiological processes and requires control mechanisms to safeguard proper timely action. We have previously described how negative regulation of TGFβ signaling is controlled by the serine/threonine kinase salt-inducible 1 (SIK1). SIK1 forms complexes with type I receptor inhibitory Smad7 down-regulates receptor. now demonstrate that induces levels via a direct transcriptional mechanism implicates Smad proteins, we mapped putative enhancer...
Abstract Background p63 is a transcription factor with intrinsic pioneer activity and pleiotropic functions. Transforming growth β (TGFβ) signaling via activation cooperative action of canonical, SMAD, non-canonical, MAP-kinase (MAPK) pathways, elicits both anti- pro-tumorigenic properties, including cell stemness invasiveness. TGFβ activates the ΔNp63 transcriptional program in cancer cells; however, link between unmasking epigenetic landscape during tumor progression allowing chromatin...
Smad proteins are key effectors of the transforming growth factor beta (TGFbeta) signaling pathway in mammalian cells. Smads composed two highly structured and conserved domains called Mad homology 1 (MH1) 2 (MH2), which linked together by a nonconserved linker region. The recent identification phosphorylation sites binding for ubiquitin ligases regions TGFbeta bone morphogenetic protein (BMP) receptor-regulated suggested that may contribute to regulation function facilitating cross-talks...