@article{MTMT:34761990, title = {Complex formation of ML324, the histone demethylase inhibitor, with essential metal ions: Relationship between solution chemistry and anticancer activity}, url = {https://m2.mtmt.hu/api/publication/34761990}, author = {Kovács, Hilda and Jakusch, Tamás and May, Nóra Veronika and Tóth, Szilárd and Szakács, Gergely and Enyedy, Éva Anna}, doi = {10.1016/j.jinorgbio.2024.112540}, journal-iso = {J INORG BIOCHEM}, journal = {JOURNAL OF INORGANIC BIOCHEMISTRY}, volume = {255}, unique-id = {34761990}, issn = {0162-0134}, year = {2024}, eissn = {1873-3344}, pages = {112540}, orcid-numbers = {Jakusch, Tamás/0000-0003-0532-5202; May, Nóra Veronika/0000-0003-4770-4681; Enyedy, Éva Anna/0000-0002-8058-8128} } @article{MTMT:34735982, title = {Cytidine deaminases APOBEC3C and APOBEC3D promote DNA replication stress resistance in pancreatic cancer cells}, url = {https://m2.mtmt.hu/api/publication/34735982}, author = {Ubhi, Tajinder and Zaslaver, Olga and Quaile, Andrew T. and Plenker, Dennis and Cao, Pinjiang and Pham, Nhu-An and Békési, Angéla and Jang, Gun-Ho and O’Kane, Grainne M. and Notta, Faiyaz and Moffat, Jason and Wilson, Julie M. and Gallinger, Steven and Vértessy, Beáta (Grolmuszné) and Tuveson, David A. and Röst, Hannes L. and Brown, Grant W.}, doi = {10.1038/s43018-024-00742-z}, journal-iso = {NAT CANCER}, journal = {NATURE CANCER}, unique-id = {34735982}, abstract = {Gemcitabine is a potent inhibitor of DNA replication and is a mainstay therapeutic for diverse cancers, particularly pancreatic ductal adenocarcinoma (PDAC). However, most tumors remain refractory to gemcitabine therapies. Here, to define the cancer cell response to gemcitabine, we performed genome-scale CRISPR–Cas9 chemical–genetic screens in PDAC cells and found selective loss of cell fitness upon disruption of the cytidine deaminases APOBEC3C and APOBEC3D. Following gemcitabine treatment, APOBEC3C and APOBEC3D promote DNA replication stress resistance and cell survival by deaminating cytidines in the nuclear genome to ensure DNA replication fork restart and repair in PDAC cells. We provide evidence that the chemical–genetic interaction between APOBEC3C or APOBEC3D and gemcitabine is absent in nontransformed cells but is recapitulated across different PDAC cell lines, in PDAC organoids and in PDAC xenografts. Thus, we uncover roles for APOBEC3C and APOBEC3D in DNA replication stress resistance and offer plausible targets for improving gemcitabine-based therapies for PDAC. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.}, year = {2024}, eissn = {2662-1347}, orcid-numbers = {Ubhi, Tajinder/0000-0002-9107-1888; Quaile, Andrew T./0000-0002-1194-3712; Plenker, Dennis/0000-0003-3895-4064; Békési, Angéla/0000-0003-2294-3002; O’Kane, Grainne M./0000-0002-8690-403X; Wilson, Julie M./0000-0003-2510-962X; Gallinger, Steven/0000-0002-6998-9414; Brown, Grant W./0000-0002-9002-5003} } @article{MTMT:34735956, title = {Bone Marrow–Derived ABCC6 Is an Essential Regulator of Ectopic Calcification In Pseudoxanthoma Elasticum}, url = {https://m2.mtmt.hu/api/publication/34735956}, author = {Brampton, Christopher and Pomozi, Viola and Le Corre, Yannick and Zoll, Janna and Kauffenstein, Gilles and Ma, Chi and Hoffmann, Peter R. and Martin, Ludovic and Le Saux, Olivier}, doi = {10.1016/j.jid.2024.01.026}, journal-iso = {J INVEST DERMATOL}, journal = {JOURNAL OF INVESTIGATIVE DERMATOLOGY}, unique-id = {34735956}, issn = {0022-202X}, year = {2024}, eissn = {1523-1747}, orcid-numbers = {Brampton, Christopher/0009-0003-9026-181X; Le Corre, Yannick/0009-0003-4656-1006; Zoll, Janna/0009-0006-6166-0848; Kauffenstein, Gilles/0000-0003-4994-8305; Ma, Chi/0000-0002-4302-9079; Hoffmann, Peter R./0000-0003-2417-7305; Martin, Ludovic/0009-0008-4136-9601; Le Saux, Olivier/0000-0002-5605-3617} } @article{MTMT:34669504, title = {Exosomal small RNA profiling in first-trimester maternal blood explores early molecular pathways of preterm preeclampsia}, url = {https://m2.mtmt.hu/api/publication/34669504}, author = {Gál, Luca and Fóthi, Ábel and Orosz, Gergő and Nagy, Sándor and Than, Nándor Gábor and Orbán, Tamás I.}, doi = {10.3389/fimmu.2024.1321191}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {15}, unique-id = {34669504}, issn = {1664-3224}, year = {2024}, eissn = {1664-3224}, orcid-numbers = {Orbán, Tamás I./0000-0002-3424-3428} } @misc{MTMT:34577433, title = {Utilizing a dual endogenous reporter system to identify functional regulators of aberrant stem cell and differentiation activity in colorectal cancer.}, url = {https://m2.mtmt.hu/api/publication/34577433}, author = {Spisák, Sándor and Chen, David and Likasitwatanakul, Pornlada and Doan, Paul and Li, Zhixin and Bala, Pratyusha and Vizkeleti, Laura and Tisza, Viktoria and De Silva, Pushpamail and Giannakis, Marios and Wolpin, Brian and Qi, Jun and Sethi, Nilay S}, unique-id = {34577433}, abstract = {Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer (CRC). To identify functional mediators that regulate these key cellular programs in CRC, we developed an endogenous reporter system by genome-editing human CRC cell lines with knock-in fluorescent reporters at the SOX9 and KRT20 locus to report aberrant stem cell-like activity and differentiation, respectively, and then performed pooled genetic perturbation screens. Constructing a dual reporter system that simultaneously monitored aberrant stem cell-like and differentiation activity in the same CRC cell line improved our signal to noise discrimination. Using a focused-library CRISPR screen targeting 78 epigenetic regulators with 542 sgRNAs, we identified factors that contribute to stem cell-like activity and differentiation in CRC. Perturbation single cell RNA sequencing (Perturb-seq) of validated hits nominated SMARCB1 of the BAF complex (also known as SWI/SNF) as a negative regulator of differentiation across an array of neoplastic colon models. SMARCB1 is a dependency in CRC and required for in vivo growth of human CRC models. These studies highlight the utility of a biologically designed endogenous reporter system to uncover novel therapeutic targets for drug development.}, keywords = {colorectal cancer; Genome editing; Intestinal differentiation; stem cell program}, year = {2024} } @article{MTMT:34575637, title = {Direct interaction of Su(var)2-10 via the SIM-binding site of the Piwi protein is required for transposon silencing in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/34575637}, author = {Bence, Melinda and Jankovics, Ferenc and Kristó, Ildikó and Gyetvai, Akos and Vértessy, Beáta (Grolmuszné) and Erdélyi, Miklós}, doi = {10.1111/febs.17073}, journal-iso = {FEBS J}, journal = {FEBS JOURNAL}, unique-id = {34575637}, issn = {1742-464X}, abstract = {Nuclear Piwi/Piwi-interacting RNA complexes mediate co-transcriptional silencing of transposable elements by inducing local heterochromatin formation. In Drosophila, sumoylation plays an essential role in the assembly of the silencing complex; however, the molecular mechanism by which the sumoylation machinery is recruited to the transposon loci is poorly understood. Here, we show that the Drosophila E3 SUMO-ligase Su(var)2-10 directly binds to the Piwi protein. This interaction is mediated by the SUMO-interacting motif-like (SIM-like) structure in the C-terminal domain of Su(var)2-10. We demonstrated that the SIM-like structure binds to a special region found in the MID domain of the Piwi protein, the structure of which is highly similar to the SIM-binding pocket of SUMO proteins. Abrogation of the Su(var)2-10-binding surface of the Piwi protein resulted in transposon derepression in the ovary of adult flies. Based on our results, we propose a model in which the Piwi protein initiates local sumoylation in the silencing complex by recruiting Su(var)2-10 to the transposon loci.}, keywords = {SUBSTRATE; Drosophila melanogaster; Defense; MOTIF; Sumoylation; Sumoylation; SUMO; piRNA pathway; Su(var)2-10; PIWI/piRNA; ENFORCES}, year = {2024}, eissn = {1742-4658} } @article{MTMT:34575448, title = {Interaction of mycotoxins zearalenone, α-zearalenol, and β-zearalenol with cytochrome P450 (CYP1A2, 2C9, 2C19, 2D6, and 3A4) enzymes and organic anion transporting polypeptides (OATP1A2, OATP1B1, OATP1B3, and OATP2B1)}, url = {https://m2.mtmt.hu/api/publication/34575448}, author = {Kaci, Hana and Dombi, Ágnes and Gömbös, Patrik and Szabó, András and Bakos, Éva and Laczka, Csilla and Poór, Miklós}, doi = {10.1016/j.tiv.2024.105789}, journal-iso = {TOXICOL IN VITRO}, journal = {TOXICOLOGY IN VITRO}, volume = {96}, unique-id = {34575448}, issn = {0887-2333}, keywords = {ZEARALENONE; Cytochrome P450 enzymes; organic anion transporting polypeptides; α-zearalenol; β-zearalenol}, year = {2024}, eissn = {1879-3177}, orcid-numbers = {Szabó, András/0000-0002-5315-0024} } @article{MTMT:34563187, title = {Decreased Expression of Placental Proteins in Recurrent Pregnancy Loss: Functional Relevance and Diagnostic Value}, url = {https://m2.mtmt.hu/api/publication/34563187}, author = {Tóth, Eszter and Györffy, Dániel and Posta, Máté and Hupuczi, Petronella and Balogh, Andrea and Szalai, Gábor and Orosz, Gergő Balázs and Orosz, László and Szilágyi, András and Oravecz, Orsolya and Veress, Lajos and Nagy, Sándor and Török, Olga and Murthi, Padma and Erez, Offer and Papp, Zoltán and Ács, Nándor and Than, Nándor Gábor}, doi = {10.3390/ijms25031865}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {25}, unique-id = {34563187}, issn = {1661-6596}, abstract = {Miscarriages affect 50–70% of all conceptions and 15–20% of clinically recognized pregnancies. Recurrent pregnancy loss (RPL, ≥2 miscarriages) affects 1–5% of recognized pregnancies. Nevertheless, our knowledge about the etiologies and pathophysiology of RPL is incomplete, and thus, reliable diagnostic/preventive tools are not yet available. Here, we aimed to define the diagnostic value of three placental proteins for RPL: human chorionic gonadotropin free beta-subunit (free-β-hCG), pregnancy-associated plasma protein-A (PAPP-A), and placental growth factor (PlGF). Blood samples were collected from women with RPL (n = 14) and controls undergoing elective termination of pregnancy (n = 30) at the time of surgery. Maternal serum protein concentrations were measured by BRAHMS KRYPTOR Analyzer. Daily multiple of median (dMoM) values were calculated for gestational age-specific normalization. To obtain classifiers, logistic regression analysis was performed, and ROC curves were calculated. There were differences in changes of maternal serum protein concentrations with advancing healthy gestation. Between 6 and 13 weeks, women with RPL had lower concentrations and dMoMs of free β-hCG, PAPP-A, and PlGF than controls. PAPP-A dMoM had the best discriminative properties (AUC = 0.880). Between 9 and 13 weeks, discriminative properties of all protein dMoMs were excellent (free β-hCG: AUC = 0.975; PAPP-A: AUC = 0.998; PlGF: AUC = 0.924). In conclusion, free-β-hCG and PAPP-A are valuable biomarkers for RPL, especially between 9 and 13 weeks. Their decreased concentrations indicate the deterioration of placental functions, while lower PlGF levels indicate problems with placental angiogenesis after 9 weeks.}, year = {2024}, eissn = {1422-0067}, orcid-numbers = {Tóth, Eszter/0000-0001-7149-1482; Balogh, Andrea/0000-0003-0322-1522; Szilágyi, András/0000-0002-1773-6861; Murthi, Padma/0000-0003-2535-5134; Ács, Nándor/0000-0002-1919-1869} } @article{MTMT:34561052, title = {Resistance to Combined Anthracycline–Taxane Chemotherapy Is Associated with Altered Metabolism and Inflammation in Breast Carcinomas}, url = {https://m2.mtmt.hu/api/publication/34561052}, author = {Menyhart, Otilia and Fekete, János Tibor and Győrffy, Balázs}, doi = {10.3390/ijms25021063}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {25}, unique-id = {34561052}, issn = {1661-6596}, abstract = {Approximately 30% of early-stage breast cancer (BC) patients experience recurrence after systemic chemotherapy; thus, understanding therapy resistance is crucial in developing more successful treatments. Here, we investigated the mechanisms underlying resistance to combined anthracycline–taxane treatment by comparing gene expression patterns with subsequent therapeutic responses. We established a cohort of 634 anthracycline–taxane-treated patients with pathological complete response (PCR) and a separate cohort of 187 patients with relapse-free survival (RFS) data, each having transcriptome-level expression data of 10,017 unique genes. Patients were categorized as responders and non-responders based on their PCR and RFS status, and the expression for each gene was compared between the two groups using a Mann–Whitney U-test. Statistical significance was set at p < 0.05, with fold change (FC) > 1.44. Altogether, 224 overexpressed genes were identified in the tumor samples derived from the patients without PCR; among these, the gene sets associated with xenobiotic metabolism (e.g., CYP3A4, CYP2A6) exhibited significant enrichment. The genes ORAI3 and BCAM differentiated non-responders from responders with the highest AUC values (AUC > 0.75, p < 0.0001). We identified 51 upregulated genes in the tumor samples derived from the patients with relapse within 60 months, participating primarily in inflammation and innate immune responses (e.g., LYN, LY96, ANXA1). Furthermore, the amino acid transporter SLC7A5, distinguishing non-responders from responders, had significantly higher expression in tumors and metastases than in normal tissues (Kruskal–Wallis p = 8.2 × 10−20). The identified biomarkers underscore the significance of tumor metabolism and microenvironment in treatment resistance and can serve as a foundation for preclinical validation studies. © 2024 by the authors.}, keywords = {Inflammation; Inflammation; Inflammation; Humans; GENETICS; human; Drug Therapy, Combination; Antibiotics, Antineoplastic; Anthracyclines; anthracycline; anthracycline; Neoplasm Recurrence, Local; therapy resistance; tumor recurrence; Drug therapy; Taxoids; taxoid; antineoplastic antibiotic; bridged compound; Tumor microenvironment; Tumor microenvironment; combination drug therapy; Innate immune response; taxane; taxane; Bridged-Ring Compounds; inflammatory breast cancer; breast cancer (BC); inflammatory breast neoplasms}, year = {2024}, eissn = {1422-0067}, orcid-numbers = {Menyhart, Otilia/0000-0003-4129-4589; Fekete, János Tibor/0000-0002-6672-6563; Győrffy, Balázs/0000-0002-5772-3766} } @article{MTMT:34544300, title = {GTP Signaling Links Metabolism, DNA Repair, and Responses to Genotoxic Stress}, url = {https://m2.mtmt.hu/api/publication/34544300}, author = {Zhou, W. and Zhao, Z. and Lin, A. and Yang, J.Z. and Xu, J. and Wilder-Romans, K. and Yang, A. and Li, J. and Solanki, S. and Speth, J.M. and Walker, N. and Scott, A.J. and Wang, L. and Wen, B. and Andren, A. and Zhang, L. and Kothari, A.U. and Yao, Y. and Peterson, E.R. and Korimerla, N. and Werner, C.K. and Ullrich, A. and Liang, J. and Jacobson, J. and Palavalasa, S. and O'Brien, A.M. and Elaimy, A.L. and Ferris, S.P. and Zhao, S.G. and Sarkaria, J.N. and Győrffy, Balázs and Zhang, S. and Al-Holou, W.N. and Umemura, Y. and Morgan, M.A. and Lawrence, T.S. and Lyssiotis, C.A. and Peters-Golden, M. and Shah, Y.M. and Wahl, D.R.}, doi = {10.1158/2159-8290.CD-23-0437}, journal-iso = {CANCER DISCOV}, journal = {CANCER DISCOVERY}, volume = {14}, unique-id = {34544300}, issn = {2159-8274}, year = {2024}, eissn = {2159-8290}, pages = {158-175}, orcid-numbers = {Győrffy, Balázs/0000-0002-5772-3766} }