Article
Biochemistry & Molecular Biology
Julia Bauer, Nicole Cuvelier, Nada Ragab, Katja Simon-Keller, Frauke Nitzki, Natalie Geyer, Dominik S. Botermann, Dominik P. Elmer, Albert Rosenberger, Thomas A. Rando, Stefano Biressi, James A. Fagin, Dieter Saur, Christian Dullin, Hans-Ulrich Schildhaus, Walter Schulz-Schaeffer, Fritz Aberger, Anja Uhmann, Heidi Hahn
Summary: It has been found that in ERMS, the Hedgehog (HH)/GLI signaling pathway and RAS signaling pathway interact with each other, with RAS mutations able to increase proliferation and tumorigenicity by inhibiting the HH signaling pathway. In a mouse model, different RAS mutations have different effects on ERMS development.
Article
Cell Biology
Jeeho Kim, Young Jin Jeon, Sung-Chul Lim, Joohyun Ryu, Jung-Hee Lee, In-Youb Chang, Ho Jin You
Summary: Ephexin1 is highly expressed in patient tissues of colorectal cancer (CRC) and lung cancer (LC), and plays a critical role in promoting tumorigenesis through the Ras-mediated signaling pathway. Phosphorylated Ephexin1 at Ser16 and Ser18 (pSer16/18) may serve as an effective therapeutic target for CRC and LC as it interacts with oncogenic K-Ras to promote downstream MAPK signaling.
CELL DEATH & DISEASE
(2021)
Article
Biology
Ozgun Le Roux, Nicole L. K. Pershing, Erin Kaltenbrun, Nicole J. Newman, Jeffrey Everitt, Elisa Baldelli, Mariaelena Pierobon, Emanuel F. Petricoin, Christopher M. Counter
Summary: Different subsets of KRAS mutations are detected in different cancer types, and each mutation induces distinct transcriptional responses after activation. These responses may be a result of signaling differences caused by increased protein expression and specific mutation. These distinct responses have an impact on RAS mutational patterning in vivo, with different KRAS mutations preferentially inducing tumor initiation in a cell-specific manner.
Review
Oncology
Jahangir Alam, Md Nazmul Huda, Alan J. Tackett, Sayem Miah
Summary: Signaling pathways play critical roles in executing and controlling important biological processes within cells. Dysregulation of signaling pathways can modulate chromatin modifications, thereby contributing to tumorigenesis and metastasis. Understanding the role of these pathways in disease pathogenesis is crucial for developing targeted therapies.
CANCER AND METASTASIS REVIEWS
(2023)
Article
Chemistry, Multidisciplinary
Gyula Palfy, Dora K. Menyhard, Hanna Akontz-Kiss, Istvan Vida, Gyula Batta, Orsolya Toke, Andras Perczel
Summary: NMR relaxation techniques and molecular dynamics simulations were used to investigate the slow dynamics in K-Ras. A two-state conformational exchange on the ms timescale was observed in both GDP- and GTP-bound K-Ras. Furthermore, a low-populated higher energy state in GDP-loaded K-Ras was identified, which is involved in the interaction with nucleotide exchange factors and subsequent reactivation.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Dhirendra K. Simanshu, Mark R. Philips, John F. Hancock
Summary: One open question in RAS biology is the existence and role of RAS dimers in RAF dimerization and activation. The hypothesis of RAS dimers arose from the discovery of RAF kinases functioning as obligate dimers, suggesting that G-domain-mediated RAS dimerization might nucleate RAF dimer formation. This review presents evidence on RAS dimerization and discusses a recent consensus among RAS researchers that the clustering of multiple RAS proteins is not due to the stable association of G-domains, but rather to the membrane phospholipids and RAS C-terminal membrane anchors.
Article
Multidisciplinary Sciences
Zhenxing Zhang, Xin Li, Fan Yang, Chao Chen, Ping Liu, Yi Ren, Pengkai Sun, Zixiong Wang, Yongping You, Yi-Xin Zeng, Xinjian Li
Summary: This study demonstrates that DHHC9-mediated GLUT1 palmitoylation at Cys207 is essential for plasma membrane localization of GLUT1 and for tumor growth in glioblastoma cells. The findings suggest a potential therapeutic target for targeting GLUT1 in cancer treatment.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Wen-juan Li, Ying Huang, Yi-an Lin, Bao-ding Zhang, Mei-Yan Li, Yi-qin Zou, Guo-sheng Hu, Yao-hui He, Jing-jing Yang, Bing-lan Xie, Hai-hua Huang, Xianming Deng, Wen Liu
Summary: This study reveals the mechanism of PRMT1-mediated RNA alternative splicing in breast cancer. Overexpression of PRMT1 is closely associated with breast cancer cell growth, and the PRMT1 inhibitor iPRMT1 can effectively inhibit the growth of breast cancer cells, indicating the potential of PRMT1 as a therapeutic target.
Article
Cell Biology
Imran Khan, Akiko Koide, Mariyam Zuberi, Gayatri Ketavarapu, Eric Denbaum, Kai Wen Teng, J. Matthew Rhett, Russell Spencer-Smith, G. Aaron Hobbs, Ernest Ramsay Camp, Shohei Koide, John P. O'Bryan
Summary: This study discovered a compound that selectively binds to the nucleotide-free state of RAS and inhibits the signaling and transforming activity of certain RAS mutants with fast exchange rates. In cell experiments and animal models, this compound exhibited the ability to reduce tumor formation in cancer cells.
Article
Biochemistry & Molecular Biology
Cefan Zhou, Xiaoting Zhu, Nanxi Liu, Xueying Dong, Xuewen Zhang, Huili Huang, Yu Tang, Shicheng Liu, Mengyu Hu, Ming Wang, Xiaoling Deng, Shi Li, Rui Zhang, Yuan Huang, Hao Lyu, Shuai Xiao, Sang Luo, Declan William Ali, Marek Michalak, Xing-Zhen Chen, Zhentian Wang, Jingfeng Tang
Summary: FAM83A binds to β-catenin and inhibits the assembly of the destruction complex, thus preventing its phosphorylation and degradation. Abnormal activation of FAM83A is closely associated with the malignancy of pancreatic cancer.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Dong Hoon Shin, Jeong Yeon Jo, Minyoung Choi, Kyung-Hee Kim, Young-Ki Bae, Sang Soo Kim
Summary: The interaction between SIRT1 and p300 in KRAS-mutant lung cancer cells plays a critical role in tumor progression, suggesting the potential use of SIRT1 inhibitors and p300 activators in combination therapy for KRAS-mutant lung cancer patients.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Christophe Glorieux, Xiaojun Xia, Yong-Qiao He, Yumin Hu, Kelly Cremer, Annie Robert, Junchen Liu, Fen Wang, Jianhua Ling, Paul J. Chiao, Peng Huang
Summary: K-ras mutations enhance PD-L1 expression through a redox-mediated mechanism, while inhibition of the FGFR1 pathway reduces PD-L1 expression and enhances T cell-mediated tumor suppression.
Article
Chemistry, Multidisciplinary
Huixia Lu, Jordi Marti
Summary: This study proposes a computational framework to accurately assess the conformational variants of a target protein using all-atom Molecular Dynamics and Metadynamics simulations. The research focuses on the G12D mutated GTP bound oncogenic KRas-4B protein and reveals the influence of GTP-binding on the protein's stabilization and potential for opening druggable pockets. The findings provide new opportunities for designing efficient drugs.
Article
Genetics & Heredity
Bo-Kuan Wu, Szu-Chieh Mei, Elizabeth H. Chen, Yonggang Zheng, Duojia Pan
Summary: Activation of YAP results in upregulation of TET1, which interacts with TEAD to promote DNA demethylation at YAP target genes in the liver. Loss of TET1 reverses YAP-induced epigenetic and transcriptional changes, and suppresses YAP-induced hepatomegaly and tumorigenesis.
Article
Biochemistry & Molecular Biology
Ziyang Zhang, Keelan Z. Guiley, Kevan M. Shokat
Summary: Small molecules that covalently target the G12S somatic mutation in K-Ras have been discovered, suppressing its oncogenic signaling without affecting the wild-type protein. This finding provides a new approach to target a second somatic mutation in the oncogene KRAS.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Miriam Ejarque, Joan Sabadell-Basallote, Daniel Beiroa, Enrique Calvo, Noelia Keiran, Catalina Nunez-Roa, Maria del Mar Rodriguez, Fatima Sabench, Daniel del Castillo, Veronica Jimenez, Fatima Bosch, Ruben Nogueiras, Joan Vendrell, Sonia Fernandez-Veledo
Summary: The study reveals that GLP-2 plays a regulatory role in glucose metabolism and adipose tissue in obesity, highlighting the importance of adipose tissue for the beneficial effects of teduglutide.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Roxana Khatib Shahidi, Jenny M. Hoffmann, Shahram Hedjazifar, Laurianne Bonnet, Ritesh K. Baboota, Stephanie Heasman, Christopher Church, Ivet Elias, Fatima Bosch, Jeremie Boucher, Ann Hammarstedt, Ulf Smith
Summary: GREM1 accumulates intracellularly when overexpressed in the liver cells of mature mice and is apparently not normally processed/secreted. However, repeated intraperitoneal injections were without effects on body weight and insulin sensitivity and adipose tissue UCP1 levels were only marginally reduced.
Editorial Material
Genetics & Heredity
Marie-Christine Birling, Atsushi Yoshiki, David J. Adams, Shinya Ayabe, Arthur L. Beaudet, Joanna Bottomley, Allan Bradley, Steve D. M. Brown, Antje Buerger, Wendy Bushell, Francesco Chiani, Hsian-Jean Genie Chin, Skevoulla Christou, Gemma F. Codner, Francesco J. DeMayo, Mary E. Dickinson, Brendan Doe, Leah Rae Donahue, Martin D. Fray, Alessia Gambadoro, Xiang Gao, Marina Gertsenstein, Alba Gomez-Segura, Leslie O. Goodwin, Jason D. Heaney, Yann Herault, Martin Hrabe de Angelis, Si-Tse Jiang, Monica J. Justice, Petr Kasparek, Ruairidh E. King, Ralf Kuhn, Ho Lee, Young Jae Lee, Zhiwei Liu, K. C. Kent Lloyd, Isabel Lorenzo, Ann-Marie Mallon, Colin McKerlie, Terrence F. Meehan, Violeta Munoz Fuentes, Stuart Newman, Lauryl M. J. Nutter, Goo Taeg Oh, Guillaume Pavlovic, Ramiro Ramirez-Solis, Barry Rosen, Edward J. Ryder, Luis A. Santos, Joel Schick, John R. Seavitt, Radislav Sedlacek, Claudia Seisenberger, Je Kyung Seong, William C. Skarnes, Tania Sorg, Karen P. Steel, Masaru Tamura, Glauco P. Tocchini-Valentini, Chi-Kuang Leo Wang, Hannah Wardle-Jones, Marie Wattenhofer-Donze, Sara Wells, Michael V. Wiles, Brandon J. Willis, Joshua A. Wood, Wolfgang Wurst, Ying Xu, Lydia Teboul, Stephen A. Murray
Summary: The International Mouse Phenotyping Consortium has reported the generation of new mouse mutant strains for over 5,000 genes, including 2,850 new null mutations, 2,987 new conditional-ready strains, and 4,433 new reporter alleles.
Article
Multidisciplinary Sciences
Joan Bertolin, Victor Sanchez, Albert Ribera, Maria Luisa Jaen, Miquel Garcia, Anna Pujol, Xavier Sanchez, Sergio Munoz, Sara Marco, Jennifer Perez, Gemma Elias, Xavier Leon, Carles Roca, Veronica Jimenez, Pedro Otaegui, Francisca Mulero, Marc Navarro, Jesus Ruberte, Fatima Bosch
Summary: MPSIVA, a lysosomal storage disorder, causes severe skeletal and non-skeletal alterations in patients. Researchers created a MPSIVA rat model replicating human pathology and developed an AAV9-Galns gene therapy for treatment.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Giuseppe Bosso, Pablo Lanuza-Gracia, Sergio Pineiro-Hermida, Merve Yilmaz, Rosa Serrano, Maria A. Blasco
Summary: BRAF(V600E) mutation is common in cancer and its expression leads to DNA damage response, inflammation, and differential changes in cell cycle and senescence-associated proteins in lung epithelia.
CELL DEATH & DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Miriam Ayora, David Fraguas, Renzo Abregu-Crespo, Sandra Recio, Maria A. Blasco, Ana Moises, Aksinya Derevyanko, Celso Arango, Covadonga M. Diaz-Caneja
Summary: The meta-analysis found that leukocyte telomere length was significantly shorter in patients with schizophrenia and related disorders compared to healthy controls, with no significant effects of age or illness duration on this difference. The results support the hypothesis of accelerated cellular aging in schizophrenia and related disorders, highlighting the need for large longitudinal studies with repeated telomere length measurements and appropriate assessments of associated factors.
MOLECULAR PSYCHIATRY
(2022)
Article
Cell Biology
Alonso Sanchez-Cruz, Alberto Hernandez-Pinto, Concepcion Lillo, Carolina Isiegas, Miguel Marchena, Ignacio Lizasoain, Fatima Bosch, Pedro de la Villa, Catalina Hernandez-Sanchez, Enrique J. de la Rosa
Summary: Synaptic loss, neuronal death, and circuit remodeling are common features of central nervous system neurodegenerative disorders. Impaired insulin receptor signaling has been linked to retinitis pigmentosa (RP). Decreased levels of the insulin receptor and its downstream effector phospho-S6 were observed in a mouse model of RP, along with abnormal synapses between photoreceptors and other cells. Gene therapy using proinsulin restored retinal insulin receptor signaling, preserved synaptic connectivity, and prolonged visual function in RP mice.
CELL DEATH & DISEASE
(2022)
Article
Medicine, Research & Experimental
Estefania Casana, Veronica Jimenez, Claudia Jambrina, Victor Sacristan, Sergio Munoz, Jordi Rodo, Ignasi Grass, Miguel Garcia, Cristina Mallol, Xavier Leon, Alba Casellas, Victor Sanchez, Sylvie Franckhauser, Tura Ferre, Sara Marco, Fatima Bosch
Summary: This study demonstrates that treatment with liver-directed AAV-BMP7 vectors can increase BMP7 concentration, activate brown adipose tissue, enhance energy expenditure, reverse pathological changes associated with obesity, and ultimately normalize body weight and insulin resistance, providing a potential therapeutic strategy for insulin resistance, type 2 diabetes, and obesity.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Genetics & Heredity
Paula Martinez, Raul Sanchez-Vazquez, Iole Ferrara-Romeo, Rosa Serrano, Juana M. Flores, Maria A. Blasco
Summary: By generating a mouse model for the human POT1(R117C) mutation, this study found that the mutation leads to longer telomeres and exerts dominant-negative effects at telomeres. Heterozygous mice with this mutation also develop angiosarcomas, including cardiac angiosarcomas. This research provides important insights into human cancers initiated by POT1 mutations.
Article
Multidisciplinary Sciences
Sergio Pineiro-Hermida, Paula Martinez, Giuseppe Bosso, Juana Maria Flores, Sarita Saraswati, Jane Connor, Raphael Lemaire, Maria A. Blasco
Summary: Depletion of TRF1 does not lead to interstitial lung fibrosis, highlighting the relevance of alveolar type II cells in this disease.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Jorge Sanz-Ros, Nekane Romero-Garcia, Cristina Mas-Bargues, Daniel Monleon, Juozas Gordevicius, Robert T. Brooke, Mar Dromant, Ana Diaz, Aksinya Derevyanko, Ana Guio-Carrion, Aurora Roman-Dominguez, Marta Ingles, Maria A. Blasco, Steve Horvath, Jose Vina, Consuelo Borras
Summary: This study found that treatment of old animals with ADSC-sEVs derived from young animals can improve various parameters associated with aging and reduce frailty. This treatment induces proregenerative effects and reduces oxidative stress, inflammation, and senescence in muscle and kidney. Additionally, tissue epigenetic age decreases and metabolome shifts to a youth-like pattern after this treatment.
Article
Oncology
Cristina Montero-Conde, Luis Javier Leandro-Garcia, Angel M. Martinez-Montes, Paula Martinez, Francisco J. Moya, Rocio Leton, Eduardo Gil, Natalia Martinez-Puente, Sonsoles Guadalix, Maria Curras-Freixes, Laura Garcia-Tobar, Carles Zafon, Mireia Jorda, Garcilaso Riesco-Eizaguirre, Patricia Gonzalez-Garcia, Maria Monteagudo, Rafael Torres-Perez, Veronika Mancikova, Sergio Ruiz-Llorente, Manuel Perez-Martinez, Guillermo Pita, Juan Carlos Galofre, Anna Gonzalez-Neira, Alberto Cascon, Cristina Rodriguez-Antona, Diego Megias, Maria A. Blasco, Eduardo Caleiras, Sandra Rodriguez-Perales, Mercedes Robledo
Summary: Comprehensive molecular studies were conducted on thyroid tumors to identify prognostic biomarkers. Telomere-related alterations, especially TERT and TERC, were found in aggressive tumors. Short telomeres led to reorganization in the 5p subtelomeric region, resulting in increased gene upregulation and a more relaxed chromatin configuration in the tumors.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Carlos Lopez-Otin, Maria A. Blasco, Linda Partridge, Manuel Serrano, Guido Kroemer
Summary: Aging is driven by hallmarks that manifest with age, accelerate aging when accentuated experimentally, and can be decelerated, stopped, or reversed with therapeutic interventions. The twelve proposed hallmarks of aging include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These hallmarks are interconnected with each other and with the recently proposed hallmarks of health.
Article
Biochemistry & Molecular Biology
Sergio Pineiro-Hermida, Giuseppe Bosso, Raul Sanchez-Vazquez, Paula Martinez, Maria A. Blasco
Summary: Non-small cell lung cancer (NSCLC) is a leading cause of cancer death, and tumor progression is influenced by the interaction between cancer cells and the tumor microenvironment. Increased copy number and mRNA expression of TERT, a catalytic subunit of telomerase, is associated with decreased survival in NSCLC patients. Targeting telomeres may be an effective therapeutic approach in NSCLC treatment.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Cell Biology
Paula Martinez, Raul Sanchez-Vazquez, Arpita Saha, Maria S. Rodriguez-Duque, Sara Naranjo-Gonzalo, Joy S. Osorio-Chavez, Ana V. Villar-Ramos, Maria A. Blasco
Summary: The severity of COVID-19 increases with age, suggesting that organismal aging contributes to its fatality. Previous studies have shown that COVID-19 severity is correlated with shorter telomeres in patient's leukocytes. Lung injury is a prominent feature of acute SARS-CoV-2 infection, which can progress to lung fibrosis. In this study, we found that post-COVID-19 patients have shorter telomeres and increased lung fibrosis compared to age-matched controls with lung cancer, suggesting a link between short telomeres in ATII cells and long-term lung fibrosis in post-COVID-19 patients.