A5048711607- Melanoma and MAPK Pathways
- Protein Kinase Regulation and GTPase Signaling
- Cellular transport and secretion
- Peptidase Inhibition and Analysis
- Histone Deacetylase Inhibitors Research
- Ion channel regulation and function
- Lung Cancer Treatments and Mutations
- PI3K/AKT/mTOR signaling in cancer
- Cell Adhesion Molecules Research
- Calcium signaling and nucleotide metabolism
- Cancer-related Molecular Pathways
- Cancer Mechanisms and Therapy
- Erythrocyte Function and Pathophysiology
- Neuroscience and Neural Engineering
- Retinal Development and Disorders
- Cancer therapeutics and mechanisms
- Ion Channels and Receptors
- Cellular Mechanics and Interactions
- Lung Cancer Research Studies
- Signaling Pathways in Disease
- Occupational and environmental lung diseases
- Head and Neck Anomalies
- Neuroscience and Neuropharmacology Research
- Pluripotent Stem Cells Research
- Cell death mechanisms and regulation
Ruhrlandklinik
2017-2024
University of Duisburg-Essen
2022
Hungarian Academy of Sciences
2009-2021
HUN-REN Wigner Research Centre for Physics
2021
Eötvös Loránd University
2018
Medical University of Vienna
2015-2017
Comprehensive Cancer Center Vienna
2016-2017
HUN-REN Research Centre for Natural Sciences
2012-2015
Semmelweis University
2013
Odense University Hospital
2013
Abstract Background Inhibition of mutant KRAS challenged cancer research for decades. Recently, allele-specific inhibitors were approved the treatment KRAS-G12C lung cancer. However, de novo and acquired resistance limit their efficacy several combinations are in clinical development. Our study shows potential combining G12C with farnesyl-transferase inhibitors. Methods Combinations clinically tested on human lung, colorectal pancreatic adenocarcinoma cells vitro 2D, 3D subcutaneous...
Abstract We are interested in two aspects of a given type metastatic breast cancer: which potentially cancer‐relevant genes expressed and factors determine invasiveness. Using reverse transcription real‐time PCR, we detected gene expression 26 matrix metalloproteinases (MMPs) MDA‐MB‐231 cancer cells, including those MMP‐12, MMP‐16 variant 2, MMP‐19, MMP‐20, MMP‐21, MMP‐23, MMP‐24, MMP‐25, MMP‐25 MMP‐L1, MMP‐26, MMP‐27, MMP‐28, contrast to the 13 MMPs until now these cells. found that MMP at...
Sarcomas with an EWSR1::POU2AF3(COLCA2) fusion are a very recently described entity of preferentially sinonasal origin and undifferentiated round/spindle cell morphology. We established novel line (PF1095) carrying EWSR1::POU2AF3 from the malignant pleural effusion 25-year-old sarcoma patient. The patient was first diagnosed poorly differentiated neuroendocrine carcinoma based on tumor morphology positivity to markers such as EMA, synaptophysin, CD56. Later, EWSR1 translocation identified in...
Plasma membrane calcium pumps differentially affect the pattern of signals.
Remodeling of Ca2+ signaling is an important step in cancer progression, and altered expression members the toolkit including plasma membrane ATPases (PMCA proteins encoded by ATP2B genes) common tumors. In this study PMCAs were examined breast datasets a variety cell lines representing different subtypes. We investigated how estrogen receptor alpha (ER-α) histone deacetylase (HDAC) inhibitors regulate these pumps. Three distinct displayed significantly lower ATP2B4 mRNA invasive tissue...
Cellular calcium signaling plays important roles in several signal transduction pathways that control proliferation, differentiation and apoptosis. In epithelial cells is initiated mainly by release from endoplasmic-reticulum-associated intracellular pools. Because accumulated the endoplasmic reticulum sarco/endoplasmic ATPases (SERCA), these enzymes play a critical role of calcium-dependent cell activation, growth survival. We investigated modulation SERCA expression function human lung...
Oncogenic mutations of BRAF lead to constitutive ERK activity that supports melanoma cell growth and survival. While Ca 2+ signaling is a well‐known regulator tumor progression, the crosstalk between Ras‐BRAF‐MEK‐ERK pathway much less explored. Here we show in mutant cells abundance plasma membrane ATPase isoform 4b (PMCA4b, ATP2B4) low at baseline but markedly elevated by treatment with specific inhibitor vemurafenib. In line these findings gene expression microarray data also shows...
Plasma membrane Ca2+ ATPases (PMCAs) are known targets of phosphatidylinositol-4,5-bisphosphate (PIP2), but if and how they control the PIP2 pool has not been considered. We demonstrate here that PMCAs protect in plasma membrane. Comparison active inactive indicates protection operates by 2 mechanisms; one requiring PMCA, other not. It appears mechanism activity is removal required for sustained phospholipase C (PLC) activity, while binding. show PMCA overexpressing cells, binding can lead...
Several new therapeutic options emerged recently to treat metastatic melanoma; however, the high frequency of intrinsic and acquired resistance among patients shows a need for options. Previously, we identified plasma membrane Ca2+ ATPase 4b (PMCA4b) as metastasis suppressor in BRAF-mutant melanomas found that mutant BRAF inhibition increased expression pump, which then inhibited migratory capability cells. Earlier it was also demonstrated histone deacetylase inhibitors (HDACis) upregulated...
While papillary thyroid cancer (PTC) has largely favorable prognosis, anaplastic (ATC) is a rare but extremely aggressive malignancy with grim clinical outcome. Even though new therapeutic options are emerging for ATC, additional preclinical models and novel combinations needed specific subsets of patients. We established cell line (PF49) from the malignant pleural effusion 68-year-old male patient ATC that rapidly transformed BRAF TERT promoter mutant PTC. PF49 cells demonstrated robust...
Metastatic melanoma is the most aggressive type of skin cancer. Previously, we identified plasma membrane Ca2+ pump isoform 4b (PMCA4b or ATP2B4) as a putative metastasis suppressor in BRAF mutant cells. Metastasis suppressors are often downregulated cancer, therefore, it important to identify pathways involved their degradation. Here, studied role p38 MAPK PMCA4b degradation and its effect on metastasis. We found that activation induces internalization subsequent through endo/lysosomal...
The Ca
Abstract Poloxamers are polyethylene‐polypropylene glycol linear co‐polymers. A simple matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) method has been developed for the determination of average molecular weight poloxamers. The five standard poloxamers determined by MALDI closely corresponds to that specified manufacturers, and no distribution effects were observed. Quantitation distributions based on envelope using electrospray (ES) ionization was unsuccessful. To...
We demonstrated that the plasma membrane Ca2+ ATPase PMCA4b inhibits migration and metastatic activity of BRAF mutant melanoma cells. Actin dynamics are essential for cells to move, invade metastasize, therefore, we hypothesized affected cell through remodeling actin cytoskeleton. found expression in A375 induced a profound change shape, culture morphology, displayed polarized migratory character. Along with these changes became more rounded increased cell–cell connections, lamellipodia...
Abstract: Maintenance of Ca 2+ homeostasis is essential for normal cellular function and survival. Recent evidences suggest that also an important player apoptosis. We demonstrated the plasma membrane ATPase (PMCA) isoform 4b, a key element homeostasis, was cleaved by caspase‐3 during course This cleavage PMCA removed entire regulatory region from C terminus, leaving behind 120‐kDa catalytic fragment. Since loss activity could lead to intracellular overload consequently necrotic cell death,...
Pancreatic adenocarcinoma is one of the deadliest forms cancer with no effective therapeutic options. A KRAS mutation can be found in up to 90% all pancreatic tumors, making it a promising target. The introduction new inhibitors has been milestone history mutant tumors; however, resistance limits their efficacy. Thus, options, including combination therapies, are urgently needed. Recently, we have shown that G12C farnesyl-transferase exert synergistic antitumor effects. Here, provide...
Malignant melanoma is one of the most metastatic cancer types, and despite recent success with novel treatment strategies, there still a group patients who do not respond to any therapies. Earlier, prenylation inhibitor hydrophilic bisphosphonate zoledronic acid (ZA) was found inhibit growth in vitro, but only weaker effect observed vivo due its properties. Recently, lipophilic bisphosphonates (such as BPH1222) were developed. Accordingly, for first time, we compared BPH1222 ZA eight lines...
Pleural mesothelioma (PM) is a rare disease with dismal outcome. Systemic treatment options include chemotherapy and immunotherapy, but biomarkers for personalization are missing. The only FDA-approved diagnostic biomarker the soluble mesothelin-related protein (SMRP). Krebs von den Lungen-6 (KL-6) human mucin 1 (MUC1) glycoprotein, which has shown prognostic value as in other malignancies. present study investigated whether KL-6 can serve and/or PM.Using fully-automated chemiluminescence...