Antoni G Wiedlocha
Oslo University Hospital
Receptor tyrosine kinaseImmunotoxinPhosphorylationFusion proteinChromosomal translocationFibroblast growth factor receptor 3Molecular biologyCytotoxic T cellAntibodyReceptorPlatelet-derived growth factor receptorChemistryGrowth factor receptorGrowth factorEndocytosisDiphtheria toxinFibroblast growth factor receptor 1Cancer researchMonoclonal antibodyBiochemistrySignal transductionFibroblast growth factorIntracellularFibroblast growth factor receptorBiologyCell biologyCytosol
Publications 53
#1Antoni Wiedlocha (Oslo University Hospital)H-Index: 12
For multi-cellular organisms to organize tissues, their cells must communicate with each other [...]
#1Karolina Jendryczko (UWr: University of Wrocław)
#2Julia Chudzian (UWr: University of Wrocław)H-Index: 2
Last. Anna Szlachcic (UWr: University of Wrocław)H-Index: 10
view all 8 authors...
Fibroblast growth factor receptors (FGFRs) are emerging targets for directed cancer therapy. Presented here is a new FGFR1-targeting conjugate, the peptibodyF2, which employs peptibody, a fusion of peptide and the Fc fragment of human IgG as a selective targeting agent and drug carrier. Short peptide based on FGF2 sequence was used to construct a FGFR1-targeting peptibody. We have shown that this peptide ensures specific delivery of peptibodyF2 into FGFR1-expressing cells. In order to use peptib...
#1Michal Kostas (Oslo University Hospital)H-Index: 1
#2Agata Lampart (UWr: University of Wrocław)H-Index: 2
Last. Malgorzata Zakrzewska (UWr: University of Wrocław)H-Index: 17
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Abstract FGF1 and FGF2 bind to specific cell-surface tyrosine kinase receptors (FGFRs) and activate intracellular signaling that leads to proliferation, migration or differentiation of many cell types. Besides this classical mode of action, under stress conditions, FGF1 and FGF2 are translocated in a receptor-dependent manner via the endosomal membrane into the cytosol and nucleus of the cell. However, despite many years of research, the role of translocated FGF1 and FGF2 inside the cell remains...
15 CitationsSource
#1Michal Kostas (University of Oslo)H-Index: 6
#2Ellen Margrethe Haugsten (University of Oslo)H-Index: 15
Last. Jørgen Wesche (University of Oslo)H-Index: 24
view all 11 authors...
: Recently, FGFR1 was found to be overexpressed in osteosarcoma and represents an important target for precision medicine. However, because targeted cancer therapy based on FGFR inhibitors has so far been less efficient than expected, a detailed understanding of the target is important. We have here applied proximity-dependent biotin labeling combined with label-free quantitative mass spectrometry to identify determinants of FGFR1 activity in an osteosarcoma cell line. Many known FGFR interactor...
17 CitationsSource
#1Mateusz Adam Krzyscik (UWr: University of Wrocław)H-Index: 4
#2Malgorzata Zakrzewska (UWr: University of Wrocław)H-Index: 17
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 9 authors...
Antibody–drug conjugates (ADCs) are a new class of anticancer therapeutics that combine the selectivity of targeted treatment, ensured by monoclonal antibodies, with the potency of the cytotoxic agent. Here, we applied an analogous approach, but instead of an antibody, we used fibroblast growth factor 2 (FGF2). FGF2 is a natural ligand of fibroblast growth factor receptor 1 (FGFR1), a cell-surface receptor reported to be overexpressed in several types of tumors. We developed and characterized FG...
12 CitationsSource
The fibroblast growth factor receptors (FGFRs) are important oncogenes promoting tumor progression in many types of cancer, such as breast, bladder, and lung cancer as well as multiple myeloma and rhabdomyosarcoma. However, little is known about how these receptors are internalized and down-regulated in cells. We have here applied proximity biotin labeling to identify proteins involved in FGFR4 signaling and trafficking. For this purpose we fused a mutated biotin ligase, BirA*, to the C-terminal...
11 CitationsSource
#1Malgorzata Zakrzewska (University of Oslo)H-Index: 17
Last. Antoni Wiedlocha (Oslo University Hospital)H-Index: 12
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Fibroblast growth factor 1 (FGF1) controls cellular activities through the activation of specific cell-surface FGF receptors (FGFRs). Transphosphorylation of tyrosine residues in the kinase domain of FGFRs leads to activation of intracellular signaling cascades, including those mediated by mitogen-activated protein kinases (MAPKs). FGFRs also contain a serine-rich C-terminal tail. We identified a regulatory mechanism of FGFR signaling involving phosphorylation of Ser 777 in the C-terminal region...
37 CitationsSource
#1Anna Szlachcic (UWr: University of Wrocław)H-Index: 10
#2Katarzyna Pala (UWr: University of Wrocław)H-Index: 3
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 6 authors...
Fibroblast growth factor receptors (FGFRs) are overexpressed in a wide variety of tumors, such as breast, bladder, and prostate cancer, and therefore they are attractive targets for different types of anticancer therapies. In this study, we designed, constructed, and characterized FGFR-targeted gold nanoconjugates suitable for infrared-induced thermal ablation (localized heating leading to cancer cell death) based on gold nanoparticles (AuNPs). We showed that a recombinant ligand of all FGFRs, h...
26 CitationsSource
#1Malgorzata Zakrzewska (University of Oslo)H-Index: 17
#2Vigdis SørensenH-Index: 14
Last. Sjur Olsnes (University of Oslo)H-Index: 64
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Abstract Fibroblast growth factor 1 (FGF1) has the property to become translocated from the extracellular space into the cell cytosol and nucleus. Membrane translocation of FGF1 occurs subsequent to endocytic uptake and is strictly FGF-receptor (FGFR) dependent. Here we have investigated the timing of FGF1 translocation in relation to FGFR1 signalling. We found that the translocation of FGF1 is a periodic event that occurs with 24 h intervals. Serum-starved cells translocated the growth factor w...
8 CitationsSource
The fibroblast growth factor receptors (FGFR) play essential roles both during development and in the adult. Upon ligand binding, FGFRs induce intracellular signaling networks that tightly regulate key biological processes, such as cell proliferation, survival, migration, and differentiation. Deregulation of FGFR signaling can thus alter tissue homeostasis and has been associated with several developmental syndromes as well as with many types of cancer. In human cancer, FGFRs have been found to ...
210 CitationsSource