A5090074065- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- MicroRNA in disease regulation
- Glioma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- Microtubule and mitosis dynamics
- Hedgehog Signaling Pathway Studies
- RNA modifications and cancer
- Cancer Research and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Pluripotent Stem Cells Research
- Genomics, phytochemicals, and oxidative stress
- Wnt/β-catenin signaling in development and cancer
- Immune cells in cancer
- Melanoma and MAPK Pathways
- Genomics and Chromatin Dynamics
- Cell death mechanisms and regulation
- Hippo pathway signaling and YAP/TAZ
- RNA Interference and Gene Delivery
- Zebrafish Biomedical Research Applications
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
Karolinska Institutet
2011-2024
Princess Margaret Cancer Centre
2008-2010
Breast Cancer Research Foundation
2009
Ontario Institute for Cancer Research
2007
The Trp53 gene family member Trp73 encodes two major groups of protein isoforms, TAp73 and ΔNp73, with opposing pro- anti-apoptotic functions; consequently, their relative ratio regulates cell fate. However, the precise roles p73 isoforms in cellular events such as tumor initiation, embryonic development, death remain unclear. To determine which aspects function are attributable to we generated characterized mice exons encoding were specifically deleted create a TAp73-deficient (TAp73 −/− )...
Mice with a complete deficiency of p73 have severe neurological and immunological defects due to the absence all TAp73 DeltaNp73 isoforms. As part our ongoing program distinguish biological functions these isoforms, we generated mice that are selectively deficient for isoform. lacking (DeltaNp73(-/-) mice) viable fertile but display signs neurodegeneration. Cells from DeltaNp73(-/-) sensitized DNA-damaging agents show an increase in p53-dependent apoptosis. When analyzing DNA damage response...
The role of various p73 isoforms in tumorigenesis has been controversial. However, as we have recently shown, the generation TAp73-deficient (TAp73(-/-)) mice reveals that TAp73 exert tumor-suppressive functions, indicating an emerging for Trp-73 maintenance genomic stability. Unlike lacking all isoforms, TAp73(-/-) show a high incidence spontaneous tumors. Moreover, are infertile and produce oocytes exhibiting spindle abnormalities. These data suggest link between activities common...
The p53 target gene Wig-1 encodes a double-stranded-RNA-binding zinc finger protein. We show here that binds to mRNA and stabilizes it through an AU-rich element (ARE) in the 3′ UTR of mRNA. This effect is mirrored by enhanced protein levels both unstressed cells exposed p53-activating stress agents. Thus, previously undescribed ARE-regulating acts as positive feedback regulator p53, with implications for steady-state response. Our data reveal link between tumor suppressor...
Scientific Report5 March 2014Open Access MYC proteins promote neuronal differentiation by controlling the mode of progenitor cell division Nikolay Zinin Department Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden Search for more papers this author Igor Adameyko Medical Biochemistry Biophysics (MBB), Margareta Wilhelm Nicolas Fritz Per Uhlén Patrik Ernfors Marie Arsenian Henriksson Corresponding Author Information Zinin1,‡, Adameyko2,‡, Wilhelm1, Fritz2,...
Significance Angiogenesis, the development of blood vessels within a solid tumor, is not only essential for primary tumor growth but also vital invasion and metastasis. The TP73 gene, p53-family encodes both suppressor, TAp73, an oncogene, ΔNp73. Here we report that TAp73 ΔNp73 have opposing roles in angiogenesis. Loss or upregulation leads to highly vascularized tumors found correlate with increased angiogenesis patients breast cancer. Furthermore, show suppress proangiogenic cytokines...
Abstract In this study, we take advantage of human induced pluripotent stem (iPS) cell-derived neural cells and brain organoids to study the role p53 during development. We knocked down (KD) in neuroepithelial (NES) derived from iPS cells. Upon p53KD, NES rapidly show centrosome amplification genomic instability. Furthermore, a reduced proliferation rate, downregulation genes involved oxidative phosphorylation (OXPHOS), an upregulation glycolytic capacity was apparent upon loss p53....
Significance Breast cancer is one of the most prevalent cancers worldwide. Understanding this complex disease therefore great importance. Here, we report that loss TAp73, a known tumor suppressor and member p53 protein family, leads to increased activation NF-κB pathway, secretion chemokine CCL2, an increase in protumoral macrophage infiltration human breast cancer. Both high levels CCL2 are correlate with poor prognosis patients. This study identifies TAp73 as regulator recruitment...
Abstract Hyperproliferating cancer cells produce energy mainly from aerobic glycolysis, which results in elevated ROS levels. Thus aggressive tumors often possess enhanced anti-oxidant capacity that impedes many current anti-cancer therapies. Additionally, ROS-compromised ubiquitin proteasome system (UPS) is deregulated for timely removal of oxidized proteins, thus enabling cell survival. Taken UPS maintains the turnover factors controlling cycle and apoptosis – such as p53 or p73, it...
Significance Here we describe and utilize a model of medulloblastoma, malignancy accounting for 20% all childhood brain cancers. We used iPS-derived neural stem cells with familial mutation causing aberrant SHH signaling. show that these cells, when transplanted into mouse cerebellum, form tumors mimics SHH-driven demonstrating the development cancer from healthy in vivo. Our results reprogramming somatic carrying mutations can be to initiation progression cancer.
Receptor-interacting protein 2 (RIP2), also known as CARDIAK and RICK, has been reported to play a role in both adaptive T cell responses innate immunity mediator TLR signaling nucleotide-binding oligomerization domain (Nod) signaling. Because initial reports remain controversial, we have further examined immune RIP2-deficient mice on the C57BL/6 background. Despite up-regulation of RIP2 after activation, could not detect any defect proliferation or Th1/Th2 RIP2-KO mice. Furthermore, found...
Abstract Medulloblastoma (MB) is one of the most common malignant brain tumors in children. Current preclinical vivo model systems for MB have increased our understanding molecular mechanisms regulating development; however, they may not be suitable high-throughput screening efforts. We demonstrate here that transplantation seven different cell lines or patient-derived cells into blastula stage zebrafish embryos leads to orthotopic tumor growth can observed within 24 hours after...
Medulloblastoma (MB) is one of the most common malignant brain tumors in children. Current preclinical vivo model systems for MB have increased our understanding molecular mechanisms regulating development. However, they may not be suitable large-scale studies. The aim this study was to investigate if a zebrafish-based xenograft can recapitulate growth and enable rapid drug testing.
Abstract Current treatment modalities for disseminated cutaneous malignant melanoma (CMM) improve survival; however, relapses are common. A number of receptor tyrosine kinases (RTKs) including EGFR and MET have been reported to be involved in CMM metastasis the development resistance therapy, targeting mitogen-activated protein kinase (MAPK pathway). IHC analysis showed that patients with higher expression had a significantly shorter overall survival. In addition, silencing caused an...
X-ray in-line phase contrast has recently been combined with CO2 angiography for high-resolution small-animal vascular imaging at low radiation dose. In this paper we further investigate the potential and limitations of method demonstrate observation vessels down to 8 μm in diameter, considerably smaller than 60 previously reported. Our phase-contrast system is based on a liquid-metal-jet-anode x-ray source utilizes free-space propagation convert shifts, caused by refractive index...
Multidrug resistance (MDR) is a major cause of treatment failure. In cancer cells, MDR often caused by an increased efflux therapeutic drugs mediated up-regulation ATP binding cassette (ABC) transporters. It has previously been shown that oncogenic ΔNp73 plays important role in chemo-resistance. Here we aimed at unraveling the regulating multidrug breast and melanoma cells. KEGG pathway analysis was used to identify pathways enriched samples with high expression. We found ABC transporter...
Preservation of blood vessel integrity, which is critical for normal physiology and organ function, controlled at multiple levels, including endothelial junctions. However, the mechanism that controls adequate assembly cell junctions not fully defined. Here, we uncover TAp73 transcription factor as a vascular architect orchestrates transcriptional programs involved in junction establishment developmental morphogenesis identify Angiomotin (AMOT) direct target. Knockdown p73 cells only results...