Article
Cell Biology
Isabella N. Brown, M. Carmen Lafita-Navarro, Maralice Conacci-Sorrell
Summary: The nucleolus plays a crucial role in protein synthesis by producing new ribosomes. In cancer, nucleolar activity is heightened due to increased demand for protein synthesis. The transcription factor MYC promotes nucleolar activity and understanding and potentially inhibiting aberrant nucleolar activity in cancer cells could lead to novel therapeutics.
Review
Biochemistry & Molecular Biology
Ping Song, Fan Yang, Hongchuan Jin, Xian Wang
Summary: In addition to gene regulation and post-translational modifications, abnormal translation from mRNAs to proteins is essential in cancer pathogenesis. Targeting mRNA translation presents a potential strategy for cancer treatment. Modulation of protein translation involves factors such as initiation factors, RNA-binding proteins, mRNA modifications like m(6)A, and noncoding RNAs like microRNAs and long noncoding RNAs. This review highlights the interplay between mRNA modifications and ncRNAs in regulating protein translation, offering insights for precision therapy in human cancers.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Neurosciences
Bekir Altas, Andrea J. Romanowski, Garrett W. Bunce, Alexandros Poulopoulos
Summary: The subcellular localization of mTOR in neurons has significant implications for nervous system development, function, and disease. The model of mTOR outposts suggests that localized signaling is selected and amplified through these structures.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biotechnology & Applied Microbiology
Xiaoyu Yang, Bo Song, Jie Cui, Lina Wang, Shuoshuo Wang, Linlin Luo, Lei Gao, Beixin Mo, Yu Yu, Lin Liu
Summary: This study reveals that translational reprogramming plays an important role in rice's response to salt stress, with the salt-tolerant cultivar SR86 adopting a more flexible translational adaptive strategy compared to the salt-sensitive cultivar NB. The differences in translational dynamics under salt stress between NB and SR86 may be due to their varying levels of ribosome stalling.
Correction
Cell Biology
Remi-Martin Laberge, Yu Sun, Arturo V. Orjalo, Christopher K. Patil, Adam Freund, Lili Zhou, Samuel C. Curran, Albert R. Davalos, Kathleen A. Wilson-Edell, Su Liu, Chandani Limbad, Marco Demaria, Patrick Li, Gene B. Hubbard, Yuji Ikeno, Martin Javors, Pierre-Yves Desprez, Christopher C. Benz, Pankaj Kapahi, Peter S. Nelson, Judith Campisi
Summary: Correction to the paper has been published.
NATURE CELL BIOLOGY
(2021)
Article
Hematology
Jan-Erik Messling, Karl Agger, Kasper L. Andersen, Kristina Kromer, Hanna M. Kuepper, Anders H. Lund, Kristian Helin
Summary: Novel therapies are urgently needed for the treatment of acute myeloid leukemia (AML). A study identified RIOK2 as a potential target for AML treatment, as its loss leads to decreased protein synthesis and apoptosis in leukemic cells.
Article
Biochemistry & Molecular Biology
Haoran Duan, Siqiong Zhang, Yoram Zarai, Rupert Ollinger, Yanmeng Wu, Li Sun, Cheng Hu, Yaohui He, Guiyou Tian, Roland Rad, Xiangquan Kong, Yabin Cheng, Tamir Tuller, Dieter A. Wolf
Summary: eIF3k and eIF3l play an important role in maintaining translational capacity during cellular stress by regulating ribosome synthesis.
Article
Microbiology
Xuejing Fan, Tianyu Bao, Huaxi Yi, Zongcai Zhang, Kenan Zhang, Xin Liu, Xue Lin, Zhen Zhang, Zhen Feng
Summary: The translation efficiency of Lactobacillus rhamnosus under osmotic stress was found to be regulated through co-regulation of differentially expressed genes involved in various metabolic pathways at the translation and transcription levels. This balance between survival and growth of cells was controlled by transcription and translation mechanisms.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Cell Biology
Marianne Mercer, Seoyeon Jang, Chunyang Ni, Michael Buszczak
Summary: Regulation of mRNA translation is crucial for germ cell development and function across species, involving specific RNA binding proteins. These proteins are conserved and play similar roles in germ cells of various species, highlighting the importance of understanding the mechanisms controlling mRNA translation in germ cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Pauline Francois, Hugo Arbes, Stephane Demais, Agnes Baudin-Baillieu, Olivier Namy
Summary: Ribosome profiling, a powerful tool for studying translation regulation, suffers from a lack of standardization in the bioinformatics part, hindering result reproducibility. A unique tool has been proposed to standardize the general steps of RiboSeq analysis, aiming to unify bioinformatics pipelines for translation research.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Pharmacology & Pharmacy
Jiao Zhou, Honghan Chen, Jintao Du, Haoran Tai, Xiaojuan Han, Ning Huang, Xiaobo Wang, Hui Gong, Mingyao Yang, Hengyi Xiao
Summary: Glutamine, an important amino acid involved in energy production and redox homeostasis, plays a crucial role in the aging process. Chronic glutamine deprivation leads to cellular senescence and aging, while glutamine supplementation protects against oxidative stress-induced senescence and progeria. The activation of the Akt-mTOR pathway and impairment of autolysosome function are observed during long-term glutamine deprivation, and inhibition of this pathway rescues the autophagy impairment and cellular senescence caused by glutamine deprivation. These findings provide new insights into the connection between glutamine availability and the aging process.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Microbiology
Elizabeth B. B. Sawyer, Teresa Cortes
Summary: Ribosome profiling, a recent addition to the -omics toolkit, provides insights into the process and regulation of translation. In the case of mycobacteria, this method has led to new discoveries about translational regulation and expanded our understanding of canonical translation mechanisms.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Cell Biology
Danrui Cui, Ruirui Qu, Dian Liu, Xiufang Xiong, Tingbo Liang, Yongchao Zhao
Summary: The tumor suppressor p53 and the mTOR pathway play crucial roles in human cancer, with regulatory loops governing the balance between response to stresses or commitment to cell proliferation and survival.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Qiuyue Ma, Yuxiao Wang, Shushun Li, Jing Wen, Lu Zhu, Kunyuan Yan, Yiming Du, Shuxian Li, Liping Yan, Zhijun Xie, Yunzhou Lyu, Fei Shen, Qianzhong Li
Summary: This study conducted ribosome footprint profiling and multi-omics strategy to investigate the lipid metabolism in Acer truncatum seed development. The transcriptional and proteomic features of the oil accumulation process were characterized. Additionally, key regulators influencing lipid biosynthesis were identified, and the role of post-translational regulation in lipid metabolism was revealed.
Review
Cell Biology
Stefano Fumagalli, Mario Pende
Summary: This article reviews the potential mechanisms of S6K1's action on cell size by considering its main functional targets: substrates involved in nucleic acid and protein synthesis, fat mass accumulation, retrograde control of insulin action, senescence program, and cytoskeleton organization. The interconnection between cell size, regenerative and aging responses, in which S6K1 may be involved, is also discussed.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Michael T. Meister, Marian J. A. Groot Koerkamp, Terezinha de Souza, Willemijn B. Breunis, Ewa Frazer-Mendelewska, Mariel Brok, Jeff DeMartino, Freek Manders, Camilla Calandrini, Hinri H. D. Kerstens, Alex Janse, M. Emmy M. Dolman, Selma Eising, Karin P. S. Langenberg, Marc van Tuil, Rutger R. G. Knops, Sheila Terwisscha van Scheltinga, Laura S. Hiemcke-Jiwa, Uta Flucke, Johannes H. M. Merks, Max M. van Noesel, Bastiaan B. J. Tops, Jayne Y. Hehir-Kwa, Patrick Kemmeren, Jan J. Molenaar, Marc van de Wetering, Ruben van Boxtel, Jarno Drost, Frank C. P. Holstege
Summary: This study successfully generated a collection of 19 pediatric RMS tumor organoid models, including all major subtypes. For aggressive tumors, the models can be established within a relatively short period of time and utilized for personalized drug screening. The models closely resemble the original tumors and maintain genetic stability over extended culture periods.
EMBO MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Yuval Malka, Ferhat Alkan, Shinyeong Ju, Pierre-Rene Korner, Abhijeet Pataskar, Eldad Shulman, Fabricio Loayza-Puch, Julien Champagne, Casper Wenzel, William James Faller, Ran Elkon, Cheolju Lee, Reuven Agami
Summary: The use of alternative promoters, splicing, and cleavage and polyadenylation (APA) generates uncapped and polyadenylated transcripts (5' UPTs) that expand transcriptome diversity. These transcripts resist degradation due to structured RNA and N6-methyladenosine modification. 5' UPTs appear downstream of APA sites and are induced upon APA activation.
Article
Oncology
Ianthe A. E. M. van Belzen, Marc van Tuil, Shashi Badloe, Eric Strengman, Alex Janse, Eugene T. P. Verwiel, Douwe F. M. van der Leest, Sam de Vos, John Baker-Hernandez, Alissa Groenendijk, Ronald de Krijger, Hindrik H. D. Kerstens, Jarno Drost, Marry M. Van den Heuvel-Eibrink, Bastiaan B. J. Tops, Frank C. P. Holstege, Patrick Kemmeren, Jayne Y. Hehir-Kwa
Summary: This study investigates the mutational mechanisms and functional effects of chromosomal alterations in Wilms tumors (WTs), particularly the 1q gain. By integrating genomic data and expression data, subgroups of tumors with 1q gain were identified, and differences in functional effects and mutational mechanisms were observed. The findings suggest that incorporating expression data could improve the clinical utility of 1q gain in risk stratification.
Editorial Material
Oncology
Xiangli Jiang, Fabricio Loayza-Puch
CANCER BIOLOGY & MEDICINE
(2022)
Article
Biology
Marlies C. Ludikhuize, Sira Gevers, Nguyen T. B. Nguyen, Maaike Meerlo, S. Khadijeh Shafiei Roudbari, M. Can Gulersonmez, Edwin C. A. Stigter, Jarno Drost, Hans Clevers, Boudewijn M. T. Burgering, Maria J. Rodriguez Colman
Summary: In p53-deficient colorectal cancer organoids, 5-fluorouracil induces pyrimidine imbalance, which leads to DNA damage and cell death. Rewiring glucose metabolism through PDK inhibition by DCA enhances 5-FU toxicity in glycolytic p53-deficient organoids. This has important implications for improving chemotherapy strategies for colorectal cancer, and p53 emerges as a key factor in determining the response to 5-FU.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Angela L. Caipa L. Garcia, Jill E. E. Kucab, Halh Al-Serori, Rebekah S. S. Beck, Franziska Fischer, Matthias Hufnagel, Andrea Hartwig, Andrew Floeder, Silvia Balbo, Hayley Francies, Mathew Garnett, Meritxell Huch, Jarno Drost, Matthias Zilbauer, Volker M. M. Arlt, David H. H. Phillips
Summary: Human organoids derived from different tissues have the ability to metabolize the environmental carcinogen benzo[a]pyrene. The response and metabolite formation of the organoids varied between tissue types. This study demonstrates the potential of organoids for studying environmental carcinogenesis and genetic toxicology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Adva Kochavi, Domenica Lovecchio, William James Faller, Reuven Agami
Summary: mRNA translation is altered in cancer to promote cancer development and can be targeted for immunotherapy. Ribosome heterogeneity and alternative responses to nutrient shortages in cancer cells may result in therapeutic targets such as cancer-specific peptides. This review will assess the underlying mechanisms of proteome diversification in cancer cells due to alterations in mRNA translation.
Review
Oncology
Amy B. Hont, Benoit Dumont, Kathryn S. Sutton, John Anderson, Alex Kentsis, Jarno Drost, Andrew L. Hong, Arnauld Verschuur
Summary: This review summarizes the role of various immunomodulating elements in the tumor microenvironment of pediatric renal tumors, including Wilms tumor. It discusses the roles of innate and adaptive immune cells, as well as immunomodulatory cytokines and proteins. The expression and predictive role of checkpoint modulators like PD-L1 and immunomodulating proteins like glypican-3, B7-H3, COX-2 are highlighted, with a focus on potential therapeutic innovations. Preclinical models and clinical trials of immunomodulating strategies, such as monoclonal antibodies and CAR-T cells, for relapsed/refractory/progressive pediatric renal tumors are also discussed.
PEDIATRIC BLOOD & CANCER
(2023)
Article
Oncology
Abhijeet Pataskar, Jasmine Montenegro Navarro, Reuven Agami
Summary: ABPEPserver is an online database and analytical platform that visualizes a large-scale tumor proteomics analysis of Substitutant expression across eight tumor types sourced from the CPTAC database. It offers gene-association signature analysis of Substitutant peptides, comparison of enrichment between tumor and tumor-adjacent normal tissues, and a list of candidate peptides for immunotherapy design.
Article
Cell Biology
Thomas Sell, Christian Klotz, Matthias M. Fischer, Rosario Astaburuaga-Garcia, Susanne Krug, Jarno Drost, Hans Clevers, Christine Sers, Markus Morkel, Nils Bluethgen
Summary: Colorectal cancer progression is closely related to deregulation of intestinal differentiation trajectory. The sequential mutations of APC, KRAS, TP53, and SMAD4 enable oncogenic signaling and establish cancer hallmarks. Mass cytometry of isogenic human colon and patient-derived cancer organoids reveals a differentiation axis from normal to cancer states, shaped by the driver mutations. Cells along this axis can be influenced by subsequent mutations to promote or restrict stem cell properties. Nodes of the cancer cell signaling network remain coupled to the differentiation state. Single-cell RNA sequencing links protein signaling network to transcriptomic states with biological and clinical importance.
JOURNAL OF CELL BIOLOGY
(2023)
Review
Oncology
Tessa Banki, Jarno Drost, Marry M. M. van den Heuvel-Eibrink, Annelies M. C. Mavinkurve-Groothuis, Ronald R. R. de Krijger
Summary: This study reviewed the molecular changes in nephrogenic rests (NR), which are believed to be precursor lesions of Wilms tumors (WT), the most common malignant childhood renal tumors, from 1990 to 2022. The findings showed that two genes, WT1 and WTX, and two chromosomal regions, 11p13 and 11p15, were mutated or showed loss of imprinting in both NR and WT, suggesting their potential roles in early tumorigenesis.
Editorial Material
Oncology
Cinthia Claudia Amaya Ramirez, Fabricio Loayza-Puch
Review
Urology & Nephrology
Daniela Perotti, Richard D. Williams, Jenny Wegert, Jack Brzezinski, Mariana Maschietto, Sara Ciceri, David Gisselsson, Samantha Gadd, Amy L. Walz, Rhoikos Furtwaengler, Jarno Drost, Reem Al-Saadi, Nicholas Evageliou, Saskia L. Gooskens, Andrew L. Hong, Andrew J. Murphy, Michael V. Ortiz, Maureen J. O'Sullivan, Elizabeth A. Mullen, Marry M. van den Heuvel-eibrink, Conrad V. Fernandez, Norbert Graf, Paul E. Grundy, James I. Geller, Jeffrey S. Dome, Elizabeth J. Perlman, Manfred Gessler, Vicki Huff, Kathy Pritchard-Jones
Summary: The study of Wilms tumour has significantly advanced our understanding of its biology and genetics, with the development of the 'two-hit' model of tumour development and the discovery of the genetic landscape of the tumour. Efforts have also been made to find prognostic biomarkers and develop preclinical models. However, there are still many unanswered questions, such as the molecular understanding of relapse and the origins of bilateral Wilms tumour.
NATURE REVIEWS UROLOGY
(2023)
Meeting Abstract
Oncology
Karin Langenberg, Eleonora Looze, Michael Meister, Camilla Calandrini, Femke Ringnalda, Natasha Van Eijkelenburg, Miranda Dierselhuis, Ronald De Krijger, Kimberley Ober, Linda Schild, Jarno Drost, Marc Van DeWetering, Sander Van Hooff, Selma Eising, Jan Koster, Max M. Van Noesel, Jan Molenaar
PEDIATRIC BLOOD & CANCER
(2022)
Article
Endocrinology & Metabolism
Emily J. Kay, Karla Paterson, Carla Riero-Domingo, David Sumpton, J. Henry M. Dabritz, Saverio Tardito, Claudia Boldrini, Juan R. Hernandez-Fernaud, Dimitris Athineos, Sandeep Dhayade, Ekaterina Stepanova, Enio Gjerga, Lisa J. Neilson, Sergio Lilla, Ann Hedley, Grigorios Koulouras, Grace McGregor, Craig Jamieson, Radia Marie Johnson, Morag Park, Kristina Kirschner, Crispin Miller, Jurre J. Kamphorst, Fabricio Loayza-Puch, Julio Saez-Rodriguez, Massimiliano Mazzone, Karen Blyth, Michele Zagnoni, Sara Zanivan
Summary: The study reveals that the newly synthesized proline in CAFs promotes the production of tumor collagen in breast cancer xenografts, and reducing PYCR1 levels can inhibit tumor growth and metastasis. Additionally, the synthesis of collagen and proline in CAFs is epigenetically regulated by increased pyruvate dehydrogenase-derived acetyl-CoA levels.