TY - JOUR AU - Noblejas-López, M.D.M. AU - García-Gil, E. AU - Pérez-Segura, P. AU - Pandiella, A. AU - Győrffy, Balázs AU - Ocaña, A. TI - T-reg transcriptomic signatures identify response to check-point inhibitors JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 14 PY - 2024 IS - 1 PG - 14 SN - 2045-2322 DO - 10.1038/s41598-024-60819-8 UR - https://m2.mtmt.hu/api/publication/34850804 ID - 34850804 LA - English DB - MTMT ER - TY - JOUR AU - Bosnyák, Inez AU - Sadek, Mustafa AU - Ranatunga, Wasantha AU - Kozicz, Tamás AU - Morava-Kozicz, Éva TI - Normal transferrin glycosylation does not rule out severe ALG1 deficiency JF - JOURNAL OF INHERITED METABOLIC DISEASE REPORTS J2 - JIMDS REPORTS PY - 2024 SN - 2192-8304 DO - 10.1002/jmd2.12415 UR - https://m2.mtmt.hu/api/publication/34836109 ID - 34836109 AB - ALG1‐CDG is a rare, clinically variable metabolic disease, caused by the defect of adding the first mannose (Man) to N‐acetylglucosamine (GlcNAc 2 )‐pyrophosphate (PP)‐dolichol to the growing oligosaccharide chain, resulting in impaired N‐glycosylation of proteins. N‐glycosylation has a key role in functionality, stability, and half‐life of most proteins. Therefore, congenital defects of glycosylation typically are multisystem disorders. Here we report a 3‐year‐old patient with severe neurological, cardiovascular, respiratory, musculoskeletal and gastrointestinal symptoms. ALG1‐CDG was suggested based on exome sequencing and Western blot analysis. Despite her severe clinical manifestations and genetic diagnosis, serum transferrin glycoform analysis was normal. Western blot analysis of highly glycosylated proteins in fibroblasts revealed decreased intercellular adhesion molecule 1 (ICAM1), but normal lysosomal associated membrane protein 1 and 2 (LAMP1 and LAMP2) expression levels. Glycoproteomics in fibroblasts showed the presence of the abnormal tetrasacharide. Reviewing the literature, we found 86 reported ALG1‐CDG patients, but only one with normal transferrin analysis. Based on our results we would like to highlight the importance of multiple approaches in diagnosing ALG1‐CDG, as normal serum transferrin glycosylation or other biomarkers with normal expression levels can occur. LA - English DB - MTMT ER - TY - JOUR AU - Győrffy, Balázs TI - Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors JF - INNOVATION(UNITED STATES) J2 - INNOVATION(UNITED STATES) VL - 5 PY - 2024 IS - 3 PG - 9 SN - 2666-6758 DO - 10.1016/j.xinn.2024.100625 UR - https://m2.mtmt.hu/api/publication/34831592 ID - 34831592 N1 - Department of Biophysics, Medical School, University of Pecs, Pecs, 7624, Hungary Department of Bioinformatics, Semmelweis University, Budapest, 1094, Hungary Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, 1117, Hungary Export Date: 6 May 2024 Correspondence Address: Győrffy, B.; Department of Biophysics, Hungary; email: gyorffy.balazs@yahoo.com LA - English DB - MTMT ER - TY - JOUR AU - Ungvári, Zoltán István AU - Ungvári, Anna Sára AU - Bianchini, Giampaolo AU - Győrffy, Balázs TI - Prognostic significance of a signature based on senescence-related genes in colorectal cancer JF - GEROSCIENCE: OFFICIAL JOURNAL OF THE AMERICAN AGING ASSOCIATION (AGE) J2 - GEROSCIENCE PY - 2024 SN - 2509-2715 DO - 10.1007/s11357-024-01164-6 UR - https://m2.mtmt.hu/api/publication/34825015 ID - 34825015 N1 - Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, United States Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States International Training Program in Geroscience, Doctoral College/Department of Public Health, Semmelweis University, Budapest, Hungary Department of Public Health, Semmelweis University, Semmelweis University, Budapest, Hungary Department of Medical Oncology, IRCCS Ospedale San Raffaele, Milan, Italy Dept. of Bioinformatics, Semmelweis University, Budapest, 1094, Hungary Dept. of Biophysics, Medical School, University of Pecs, Pecs, 7624, Hungary Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, 1117, Hungary Export Date: 6 May 2024 Correspondence Address: Ungvari, A.; Department of Public Health, Hungary; email: Ungann2004@gmail.com AB - Colorectal cancer, recognized as a quintessential age-related disease, underscores the intricate interplay between aging mechanisms and disease pathogenesis. Cellular senescence, a DNA damage-induced cellular stress response, is characterized by cell cycle arrest, the expression of an inflammatory senescence-associated secretory phenotype, and alterations in extracellular matrix metabolism. It is widely recognized as a fundamental and evolutionarily conserved mechanism of aging. Guided by geroscience principles, which assert that the pathogenesis of age-related diseases involves cellular mechanisms of aging, this study delves into the role of senescence-related genes in colon cancer progression. Leveraging a gene set reflective of senescence-associated pathways, we employed uni- and multivariate Cox proportional hazards survival analysis combined with the determination of the false discovery rate to analyze correlations between gene expression and survival. The integrated database of 1130 colon cancer specimens with available relapse-free survival time and relapse event data from ten independent cohorts provided a robust platform for survival analyses. We identified senescence-related genes associated with differential expression levels linked to shorter survival. Our findings unveil a prognostic signature utilizing cellular senescence-related genes (hazard ratio: 2.73, 95% CI 2.12-3.52, p = 6.4E - 16), offering valuable insights into survival prediction in colon cancer. Multivariate analysis underscored the independence of the senescence-related signature from available epidemiological and pathological variables. This study highlights the potential of senescence-related genes as prognostic biomarkers. Overall, our results underscore the pivotal role of cellular senescence, a fundamental mechanism of aging, in colon cancer progression. LA - English DB - MTMT ER - TY - JOUR AU - Parreno, V AU - Loubiere, V AU - Schuettengruber, B AU - Fritsch, L AU - Rawal, C C AU - Erokhin, M AU - Győrffy, Balázs AU - Normanno, D AU - Di Stefano, M AU - Moreaux, J AU - Butova, N L AU - Chiolo, I AU - Chetverina, D AU - Martinez, A-M AU - Cavalli, G TI - Transient loss of Polycomb components induces an epigenetic cancer fate JF - NATURE J2 - NATURE PY - 2024 SN - 0028-0836 DO - 10.1038/s41586-024-07328-w UR - https://m2.mtmt.hu/api/publication/34825014 ID - 34825014 N1 - Institute of Human Genetics, CNRS, University of Montpellier, Montpellier, France Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria University of Southern California, Los Angeles, CA, United States Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russian Federation Semmelweis University Department of Bioinformatics, Budapest, Hungary Department of Biophysics, Medical School, University of Pécs, Pécs, Hungary Department of Biological Hematology, CHU Montpellier, Montpellier, France UFR Medicine, University of Montpellier, Montpellier, France Cited By :1 Export Date: 8 May 2024 CODEN: NATUA Correspondence Address: Martinez, A.-M.; Institute of Human Genetics, France; email: anne-marie.martinez@igh.cnrs.fr Correspondence Address: Cavalli, G.; Institute of Human Genetics, France; email: giacomo.cavalli@igh.cnrs.fr Funding details: Ministère de l'Education Nationale, de l'Enseignement Superieur et de la Recherche, MESR Funding details: Ligue Contre le Cancer Funding details: Institut National de la Santé et de la Recherche Médicale, Inserm Funding details: Centre National de la Recherche Scientifique, CNRS Funding details: Université de Montpellier, UM Funding details: National Institutes of Health, NIH, R01GM117376 Funding details: Institut National Du Cancer, INCa, INCA-PLBIO18-362 Funding details: Russian Science Foundation, RSF, 20-74-10099 Funding details: National Science Foundation, NSF, 1751197 Funding details: European Research Council, ERC, 3DEpi Funding details: Fondation ARC pour la Recherche sur le Cancer, ARC, 216574 Funding details: Fondation pour la Recherche Médicale, FRM, EQU202303016 Funding details: Agence Nationale de la Recherche, ANR, ANR-18-CE15-0010 Funding details: H2020 Marie Skłodowska-Curie Actions, MSCA, 813327 Funding text 1: We thank Montpellier Resources Imagerie facility as well as the Drosophila facilty (both affiliated to BioCampus University of Montpellier, CNRS, INSERM, Montpellier, France). We thank A.-M. Popmihaylova for help with immunostaining of Drosophila tissues. We thank J. Drouin for discussions and advice on the manuscript. We thank E. Soler for discussions on the function of the ZEB1 protein in cancer. V.P. was supported by the EpiGenMed cluster of Excellence funding (Programme d\\u2019Investissements d\\u2019Avenir of the French Ministry of Higher Education and Research) and by la Ligue Nationale Contre le Cancer. V.L. was supported by the EpiGenMed cluster of Excellence funding (PIA of the French Ministry of Higher Education and Research). A.-M.M. was supported by the University of Montpellier and a grant from the Fondation ARC (contract no. 216574, acronym \\u2018Epicancer\\u2019). B.S. was supported by INSERM. G.C. was supported by CNRS. I.C. was supported by National Institutes of Health grant no. R01GM117376 and National Science Foundation Career no. 1751197. Research in the G.C. laboratory was supported by grants from the European Research Council (Advanced Grant 3DEpi), the European CHROMDESIGN ITN project (Marie Sk\\u0142odowska-Curie grant agreement no. 813327), the European E-RARE NEURO DISEASES grant \\u2018IMPACT\\u2019, by the Agence Nationale de la Recherche (PLASMADIFF3D, grant no. ANR-18-CE15-0010), by the Fondation pour la Recherche M\\u00E9dicale (grant no. EQU202303016), by the MSD Avenir Foundation ((Project GENE-IGH) and by the French National Cancer Institute (INCa, PIT-MM grant no. INCA-PLBIO18-362). M.E. was supported by RSF grant no. 20-74-10099. AB - Although cancer initiation and progression are generally associated with the accumulation of somatic mutations1,2, substantial epigenomic alterations underlie many aspects of tumorigenesis and cancer susceptibility3-6, suggesting that genetic mechanisms might not be the only drivers of malignant transformation7. However, whether purely non-genetic mechanisms are sufficient to initiate tumorigenesis irrespective of mutations has been unknown. Here, we show that a transient perturbation of transcriptional silencing mediated by Polycomb group proteins is sufficient to induce an irreversible switch to a cancer cell fate in Drosophila. This is linked to the irreversible derepression of genes that can drive tumorigenesis, including members of the JAK-STAT signalling pathway and zfh1, the fly homologue of the ZEB1 oncogene, whose aberrant activation is required for Polycomb perturbation-induced tumorigenesis. These data show that a reversible depletion of Polycomb proteins can induce cancer in the absence of driver mutations, suggesting that tumours can emerge through epigenetic dysregulation leading to inheritance of altered cell fates. LA - English DB - MTMT ER - TY - JOUR AU - Kengyel, András Miklós AU - Palarz, Philip M AU - Krohn, Jacqueline AU - Marquardt, Anja AU - Greve, Johannes N AU - Heiringhoff, Robin AU - Jörns, Anne AU - Manstein, Dietmar J TI - Motor properties of Myosin 5c are modulated by tropomyosin isoforms and inhibited by pentabromopseudilin JF - FRONTIERS IN PHYSIOLOGY J2 - FRONT PHYSIOL VL - 15 PY - 2024 PG - 13 SN - 1664-042X DO - 10.3389/fphys.2024.1394040 UR - https://m2.mtmt.hu/api/publication/34797930 ID - 34797930 N1 - * Megosztott szerzőség AB - Myosin 5c (Myo5c) is a motor protein that is produced in epithelial and glandular tissues, where it plays an important role in secretory processes. Myo5c is composed of two heavy chains, each containing a generic motor domain, an elongated neck domain consisting of a single α-helix with six IQ motifs, each of which binds to a calmodulin (CaM) or a myosin light chain from the EF-hand protein family, a coiled-coil dimer-forming region and a carboxyl-terminal globular tail domain. Although Myo5c is a low duty cycle motor, when two or more Myo5c-heavy meromyosin (HMM) molecules are linked together, they move processively along actin filaments. We describe the purification and functional characterization of human Myo5c-HMM co-produced either with CaM alone or with CaM and the essential and regulatory light chains Myl6 and Myl12b. We describe the extent to which cofilaments of actin and Tpm1.6, Tpm1.8 or Tpm3.1 alter the maximum actin-activated ATPase and motile activity of the recombinant Myo5c constructs. The small allosteric effector pentabromopseudilin (PBP), which is predicted to bind in a groove close to the actin and nucleotide binding site with a calculated ΔG of -18.44 kcal/mol, inhibits the motor function of Myo5c with a half-maximal concentration of 280 nM. Using immunohistochemical staining, we determined the distribution and exact localization of Myo5c in endothelial and endocrine cells from rat and human tissue. Particular high levels of Myo5c were observed in insulin-producing β-cells located within the pancreatic islets of Langerhans. LA - English DB - MTMT ER - TY - JOUR AU - Halász, Henriett AU - Tárnai, Viktória AU - Matkó, J AU - Nyitrai, Miklós AU - Szabó-Meleg, Edina TI - Cooperation of Various Cytoskeletal Components Orchestrates Intercellular Spread of Mitochondria between B-Lymphoma Cells through Tunnelling Nanotubes JF - CELLS J2 - CELLS-BASEL VL - 13 PY - 2024 IS - 7 PG - 23 SN - 2073-4409 DO - 10.3390/cells13070607 UR - https://m2.mtmt.hu/api/publication/34777718 ID - 34777718 N1 - Department of Biophysics, Medical School, University of Pécs, Pécs, H-7624, Hungary Department of Immunology, Faculty of Science, Eötvös Loránd University, Budapest, H-1117, Hungary Export Date: 22 April 2024 Correspondence Address: Szabó-Meleg, E.; Department of Biophysics, Hungary; email: edina.meleg@aok.pte.hu AB - Membrane nanotubes (NTs) are dynamic communication channels connecting spatially separated cells even over long distances and promoting the transport of different cellular cargos. NTs are also involved in the intercellular spread of different pathogens and the deterioration of some neurological disorders. Transport processes via NTs may be controlled by cytoskeletal elements. NTs are frequently observed membrane projections in numerous mammalian cell lines, including various immune cells, but their functional significance in the ‘antibody factory’ B cells is poorly elucidated. Here, we report that as active channels, NTs of B-lymphoma cells can mediate bidirectional mitochondrial transport, promoted by the cooperation of two different cytoskeletal motor proteins, kinesin along microtubules and myosin VI along actin, and bidirectional transport processes are also supported by the heterogeneous arrangement of the main cytoskeletal filament systems of the NTs. We revealed that despite NTs and axons being different cell extensions, the mitochondrial transport they mediate may exhibit significant similarities. Furthermore, we found that microtubules may improve the stability and lifespan of B-lymphoma-cell NTs, while F-actin strengthens NTs by providing a structural framework for them. Our results may contribute to a better understanding of the regulation of the major cells of humoral immune response to infections. LA - English DB - MTMT ER - TY - JOUR AU - Rosano, Dalia AU - Sofyali, Emre AU - Dhiman, Heena AU - Ghirardi, Chiara AU - Ivanoiu, Diana AU - Heide, Timon AU - Vingiani, Andrea AU - Bertolotti, Alessia AU - Pruneri, Giancarlo AU - Canale, Eleonora AU - Dewhurst, Hannah F AU - Saha, Debjani AU - Slaven, Neil AU - Barozzi, Iros AU - Li, Tong AU - Zemlyanskiy, Grigory AU - Phillips, Henry AU - James, Chela AU - Győrffy, Balázs AU - Lynn, Claire AU - Cresswell, George D AU - Rehman, Farah AU - Noberini, Roberta AU - Bonaldi, Tiziana AU - Sottoriva, Andrea AU - Magnani, Luca TI - Long-term Multimodal Recording Reveals Epigenetic Adaptation Routes in Dormant Breast Cancer Cells JF - CANCER DISCOVERY J2 - CANCER DISCOV VL - 14 PY - 2024 IS - 5 SP - 866 EP - 889 PG - 24 SN - 2159-8274 DO - 10.1158/2159-8290.CD-23-1161 UR - https://m2.mtmt.hu/api/publication/34763944 ID - 34763944 N1 - * Megosztott szerzőség AB - Patients with estrogen receptor-positive breast cancer receive adjuvant endocrine therapies (ET) that delay relapse by targeting clinically undetectable micrometastatic deposits. Yet, up to 50% of patients relapse even decades after surgery through unknown mechanisms likely involving dormancy. To investigate genetic and transcriptional changes underlying tumor awakening, we analyzed late relapse patients and longitudinally profiled a rare cohort treated with long-term neoadjuvant ETs until progression. Next, we developed an in vitro evolutionary study to record the adaptive strategies of individual lineages in unperturbed parallel experiments. Our data demonstrate that ETs induce nongenetic cell state transitions into dormancy in a stochastic subset of cells via epigenetic reprogramming. Single lineages with divergent phenotypes awaken unpredictably in the absence of recurrent genetic alterations. Targeting the dormant epigenome shows promising activity against adapting cancer cells. Overall, this study uncovers the contribution of epigenetic adaptation to the evolution of resistance to ETs.This study advances the understanding of therapy-induced dormancy with potential clinical implications for breast cancer. Estrogen receptor-positive breast cancer cells adapt to endocrine treatment by entering a dormant state characterized by strong heterochromatinization with no recurrent genetic changes. Targeting the epigenetic rewiring impairs the adaptation of cancer cells to ETs. LA - English DB - MTMT ER - TY - BOOK AU - Bugyi, Beáta AU - Gaszler, Péter AU - Rauan, Sakenov AU - Szütsné Tóth, Mónika Ágnes AU - Leipold Vig, Andrea TI - BioX: Math in the Lab PB - PTE ÁOK Orvosi Biológiai Intézet CY - Pécs PY - 2024 SN - 9789636262419 UR - https://m2.mtmt.hu/api/publication/34742597 ID - 34742597 N1 - Az oktatási anyag az alábbi linken lesz elérhető: https://aok.pte.hu/hu/egyseg/30/oktatas/almenu/963 LA - English DB - MTMT ER - TY - JOUR AU - Radenkovic, Silvia AU - Budhraja, Rohit AU - Klein-Gunnewiek, Teun AU - King, Alexia Tyler AU - Bhatia, Tarun N AU - Ligezka, Anna N AU - Driesen, Karen AU - Shah, Rameen AU - Ghesquière, Bart AU - Pandey, Akhilesh AU - Kasri, Nael Nadif AU - Sloan, Steven A AU - Morava-Kozicz, Éva AU - Kozicz, Tamás TI - Neural and metabolic dysregulation in PMM2-deficient human in vitro neural models. JF - CELL REPORTS J2 - CELL REP VL - 43 PY - 2024 IS - 3 PG - 25 SN - 2211-1247 DO - 10.1016/j.celrep.2024.113883 UR - https://m2.mtmt.hu/api/publication/34729568 ID - 34729568 N1 - Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, United States Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, United States Department of Human Genetics, Radboud University Medical Centre, Nijmegen, XZ 6525, Netherlands Department of Human Genetics, Emory University, Atlanta, GA 30322, United States Metabolomics Expertise Center, VIB-KU Leuven, Leuven, 3000, Belgium Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, United States Laboratory of Applied Mass Spectrometry, KU Leuven, Leuven, 3000, Belgium Manipal Academy of Higher Education (MAHE), Karnataka, Manipal, 576104, India Department of Biophysics, University of Pécs Medical School, Pécs, 7624, Hungary Department of Anatomy, University of Pécs Medical School, Pécs, 7624, Hungary Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, United States Export Date: 18 March 2024 Correspondence Address: Kozicz, T.; Department of Clinical Genomics, United States; email: tamas.kozicz@mssm.edu AB - Phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG) is a rare inborn error of metabolism caused by deficiency of the PMM2 enzyme, which leads to impaired protein glycosylation. While the disorder presents with primarily neurological symptoms, there is limited knowledge about the specific brain-related changes caused by PMM2 deficiency. Here, we demonstrate aberrant neural activity in 2D neuronal networks from PMM2-CDG individuals. Utilizing multi-omics datasets from 3D human cortical organoids (hCOs) derived from PMM2-CDG individuals, we identify widespread decreases in protein glycosylation, highlighting impaired glycosylation as a key pathological feature of PMM2-CDG, as well as impaired mitochondrial structure and abnormal glucose metabolism in PMM2-deficient hCOs, indicating disturbances in energy metabolism. Correlation between PMM2 enzymatic activity in hCOs and symptom severity suggests that the level of PMM2 enzyme function directly influences neurological manifestations. These findings enhance our understanding of specific brain-related perturbations associated with PMM2-CDG, offering insights into the underlying mechanisms and potential directions for therapeutic interventions. LA - English DB - MTMT ER -