Article
Immunology
Wancheng Liu, Meiling Gao, Lili Li, Yu Chen, Huimin Fan, Qiaomei Cai, Yueyue Shi, Chaohu Pan, Junxiao Liu, Lucy S. Cheng, Heng Yang, Genhong Cheng
Summary: SIX1 plays a crucial role in modulating tumor immunogenicity by regulating immune cell infiltration in the TME and overall survival rates of cancer patients. Its expression is negatively correlated with immune cell infiltration in TME, and it affects collagen gene expression to hinder immune cell infiltration and activation.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Songyuan Luo, Zhixu Liu, Qian Bian, Xudong Wang
Summary: The study investigates the role of Six1 in mandible development using knockout mouse models and cell experiments, revealing its critical function in regulating mandibular skeleton formation. The loss of Six1 leads to abnormal expression of osteogenic genes and affects the development of the mandible.
FRONTIERS IN GENETICS
(2023)
Article
Genetics & Heredity
Longfei Dai, Xu Wang, Tao Bai, Jianjun Liu, Bo Chen, Wenqi Yang
Summary: This study aimed to explore the effect of cellular senescence on gastric cancer and identify potential therapeutic strategies. By using cellular senescence-related genes and gastric cancer data, a prognostic risk score signature was constructed. The results showed that patients in the low-risk score group had longer survival time and were more sensitive to chemotherapy and immunotherapy.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Helena Malvezzi, Cristine Dobo, Renee Zon Filippi, Helen Mendes do Nascimento, Laura Palmieri da Silva e Sousa, Juliana Meola, Carla Azevedo Piccinato, Sergio Podgaec
Summary: The accumulation of senescent cells in endometriosis tissues is associated with an inflammatory microenvironment and the presence of pro-inflammatory markers. The expression of senescence markers varies with the phases of the menstrual cycle, and IL-1 beta levels are significantly higher in endometriosis lesions. These findings provide potential targets for therapeutic interventions to alleviate endometriosis symptoms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Valerie Janelle, Mathieu Neault, Marie-Eve Lebel, Dave Maurice De Sousa, Salix Boulet, Ludovic Durrieu, Cedric Carli, Chloe Muzac, Sebastien Lemieux, Nathalie Labrecque, Heather J. J. Melichar, Frederick A. Mallette, Jean-Sebastien Delisle
Summary: The development of T-cell dysfunction upon repeated antigen exposure involves the accumulation of DNA damage and activation of the p38MAPK signaling pathway, leading to cellular senescence features including p16(INK4a) upregulation. However, targeting p16(INK4a) can improve T-cell functionality in exhausted CAR T cells, suggesting T-cell senescence as a potential target in immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Weiwei Yuan, Yuanmin Xu, Zhiheng Wu, Yang Huang, Lei Meng, Shiping Dai, Songcheng Ying, Zhangming Chen, Aman Xu
Summary: Recent studies have shown that the high incidence and low cure rate of hepatocellular carcinoma (HCC) have not improved significantly. In this study, we aimed to establish a prognostic signature of senescence-associated genes to predict the prognosis and therapeutic response of HCC patients. We identified and constructed a relevant prognostic signature, which performed well in predicting the survival and treatment response of HCC patients.
Review
Cell Biology
Jennifer Steens, Diana Klein
Summary: Stem cells have the unique ability to self-renew and differentiate into specialized cells. Adult stem cells exhibit limited differentiation capabilities determined by their tissue of origin. HOX genes, as master regulators of cell identity and fate, play a role in embryogenesis and maintaining positional identity. Understanding the regulation of HOX genes in stem cells may lead to advancements in regenerative medicine.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Horticulture
Aung Htay Naing, May Thu Soe, Swum Yi Kyu, Chang Kil Kim
Summary: The study demonstrates that silver nanoparticles can significantly suppress ethylene production and delay petal senescence in carnations by inhibiting the expression of ethylene biosynthesis genes, a petal senescence-related gene, and genes positively regulating ethylene signaling pathway in petals and gynoecia.
SCIENTIA HORTICULTURAE
(2021)
Article
Cell Biology
Irene Lopez-Antona, Constanza Contreras-Jurado, Laura Luque-Martin, Antonio Carpintero-Leyva, Paula Gonzalez-Mendez, Ignacio Palmero
Summary: Cellular senescence has a significant impact on the regulation of the myofibroblastic phenotype in primary fibroblasts. The loss of myofibroblastic markers and functional features upon senescence implementation can be transmitted in a paracrine manner, most likely through soluble secreted factors. The Notch/TGF-beta axis is found to be the main pathway mediating the changes in the myofibroblast phenotype.
Article
Biochemistry & Molecular Biology
Ursula Foeger-Samwald, Katharina Kerschan-Schindl, Maria Butylina, Peter Pietschmann
Summary: Age-related chronic diseases, such as osteoporosis, are a significant burden to modern societies worldwide. Aging is a major risk factor for these diseases, making targeting senescence a promising option for treatment. This article focuses on recent advances in understanding senescence-related mechanisms causing age-related bone loss, and reviews treatment options targeting senescent cells for senile osteoporosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Laureline Roger, Fanny Tomas, Veronique Gire
Summary: Cellular senescence is an essentially irreversible proliferative arrest state where cells release pro-inflammatory and proteolytic factors. Different types of senescent cells accumulate in various tissues and organs with unique functions. Understanding how cells undergo extensive changes to induce a common cellular state is crucial for cancer prevention and improving health during aging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Soledad A. Camolotto, Veronika K. Belova, Luke Torre-Healy, Jeffery M. Vahrenkamp, Kristofer C. Berrett, Hannah Conway, Jill Shea, Chris Stubben, Richard Moffitt, Jason Gertz, Eric L. Snyder
Summary: The study found that HNF4α regulates the growth and molecular subtype of PDAC by activating the classical gene expression program and repressing SIX4 and SIX1.
Article
Biochemistry & Molecular Biology
Maria Florencia Mammarella, Leandro Lucero, Nosheen Hussain, Aitor Munoz-Lopez, Ying Huang, Lucia Ferrero, Guadalupe L. Fernandez-Milmanda, Pablo Manavella, Moussa Benhamed, Martin Crespi, Carlos L. Ballare, Jose Gutierrez Marcos, Pilar Cubas, Federico Ariel
Summary: The long noncoding RNA APOLO regulates the shade avoidance syndrome in Arabidopsis thaliana by dynamically modulating expression of key factors. APOLO deregulation leads to the repression of the BRC1 gene and an increase in shoot branching. It also plays a role in leaf hyponasty and influences auxin homeostasis by modulating auxin synthesis and efflux genes.
Article
Oncology
Moon Hee Yang, Timothy H. Tran, Bethany Hunt, Rebecca Agnor, Christian W. Johnson, Bing Shui, Timothy J. Waybright, Jonathan A. Nowak, Andrew G. Stephen, Dhirendra K. Simanshu, Kevin M. Haigis
Summary: An allosteric network involving lysine 104 and residues in the switch-II domain is essential for KRAS oncogenicity, which could be utilized in the development of inhibitors targeting the activated oncoprotein.
Review
Cell Biology
Jack Crouch, Maria Shvedova, Rex Jeya Rajkumar Samdavid Thanapaul, Vladimir Botchkarev, Daniel Roh
Summary: Senescence is a complex cellular stress response that leads to loss of proliferative capacity and changes in secretory pattern. Transcriptional regulation of multiple genes and epigenetic alterations to DNA and chromatin play crucial roles in the induction and maintenance of senescence. This review highlights the changes in chromatin, DNA methylation, histone alterations, and the specific epigenetic regulation of the senescence-associated secretory phenotype (SASP).
Article
Oncology
A. Fernandez Montes, E. Elez, A. Vivancos, N. Martinez, P. Gonzalez, M. Covela, J. de la Camara, A. Cousillas, J. C. Mendez, B. Grana, E. Aranda
Summary: A study found that 13% of patients had undetectable RAS mutant clones in liquid biopsy after first-line treatment, but some discrepancies between solid and liquid biopsies were observed. The results suggest a need to improve the accuracy of RAS analyses, especially in solid biopsies.
CLINICAL & TRANSLATIONAL ONCOLOGY
(2022)
Article
Oncology
Helena Verdaguer, Tamara Sauri, Daniel Alejandro Acosta, Magdalena Guardiola, Alexandre Sierra, Jorge Hernando, Paulo Nuciforo, Josep M. Miquel, Cristina Molero, Sandra Peiro, Queralt Serra-Camprubi, Guillermo Villacampa, Susana Aguilar, Ana Vivancos, Josep Tabernero, Rodrigo Dienstmann, Teresa Macarulla
Summary: Cholangiocarcinomas are highly heterogeneous at the molecular level. The classification of actionable molecular alterations according to ESCAT is associated with survival in cholangiocarcinoma patients.
CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Alba Mota, Sara S. Oltra, Pier Selenica, Cristian P. Moiola, Carlos Casas-Arozamena, Carlos Lopez-Gil, Eva Diaz, Sonia Gatius, Maria Ruiz-Miro, Ana Calvo, Alejandro Rojo-Sebastian, Pablo Hurtado, Roberto Pineiro, Eva Colas, Antonio Gil-Moreno, Jorge S. Reis-Filho, Laura Muinelo-Romay, Miguel Abal, Xavier Matias-Guiu, Britta Weigelt, Gema Moreno-Bueno
Summary: Analyzing intratumor genetic heterogeneity (ITGH) in endometrial carcinoma (EC) using sequencing technologies can help understand tumor evolution, prognosis, and guide personalized therapy. This study characterized the spatial and temporal heterogeneity of nine ECs and identified somatic mutations through whole-exome sequencing. The phylogenetic tree analysis revealed the correlation between tumor progression, prognosis, and recurrent disease, and also guided the selection of personalized therapy for a patient with ambiguous EC.
Article
Cell Biology
Dafni Chondronasiou, Diljeet Gill, Lluc Mosteiro, Rocio G. Urdinguio, Antonio Berenguer, Monica Aguilera, Sylvere Durand, Fanny Aprahamian, Nitharsshini Nirmalathasan, Maria Abad, Daniel E. Martin-Herranz, Camille Stephan Otto-Attolini, Neus Prats, Guido Kroemer, Mario F. Fraga, Wolf Reik, Manuel Serrano
Summary: A single period of OSKM expression can induce epigenetic, transcriptomic, and metabolomic changes towards a younger configuration in multiple tissues.
Article
Cell Biology
Irene Lopez-Antona, Constanza Contreras-Jurado, Laura Luque-Martin, Antonio Carpintero-Leyva, Paula Gonzalez-Mendez, Ignacio Palmero
Summary: Cellular senescence has a significant impact on the regulation of the myofibroblastic phenotype in primary fibroblasts. The loss of myofibroblastic markers and functional features upon senescence implementation can be transmitted in a paracrine manner, most likely through soluble secreted factors. The Notch/TGF-beta axis is found to be the main pathway mediating the changes in the myofibroblast phenotype.
Article
Gastroenterology & Hepatology
Marta Alonso-Nocelo, Laura Ruiz-Canas, Patricia Sancho, Kivanc Gorgulu, Sonia Alcala, Coral Pedrero, Mireia Vallespinos, Juan Carlos Lopez-Gil, Marina Ochando, Elena Garcia-Garcia, Sara Maria David Trabulo, Paola Martinelli, Patricia Sanchez-Tomero, Carmen Sanchez-Palomo, Patricia Gonzalez-Santamaria, Lourdes Yuste, Sonja Maria Wormann, Derya Kabacaoglu, Julie Earl, Alberto Martin, Fernando Salvador, Sandra Valle, Laura Martin-Hijano, Alfredo Carrato, Mert Erkan, Laura Garcia-Bermejo, Patrick C. Hermann, Hana Algul, Gema Moreno-Bueno, Christopher Heeschen, Francisco Portillo, Amparo Cano, Bruno Sainz
Summary: LOXL2 plays an important role in pancreatic ductal adenocarcinoma (PDAC), with its loss inhibiting metastasis and prolonging overall survival, while overexpression promotes tumor growth and decreases overall survival. Macrophage-secreted OSM is an inducer of LOXL2 expression, with targeting macrophages affecting its expression and collagen fiber alignment.
Editorial Material
Neurosciences
Ignacio Palmero, Vassilis Gorgoulis, Isabel Varela-Nieto
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Oncology
Ines Marin, Olga Boix, Andrea Garcia-Garijo, Isabelle Sirois, Adria Caballe, Eduardo Zarzuela, Irene Ruano, Camille Stephan-Otto Attolini, Neus Prats, Jose A. Lopez-Dominguez, Marta Kovatcheva, Elena Garralda, Javier Munoz, Etienne Caron, Maria Abad, Alena Gros, Federico Pietrocola, Manuel Serrano
Summary: Senescent cells possess various features that make them highly efficient in stimulating dendritic cells and antigen-specific CD8 T cells, including the release of alarmins, activation of IFN signaling, enhanced MHC class I machinery, and presentation of specific self-peptides. Immunization with senescent cancer cells induces strong antitumor protection mediated by DCs and CD8 T cells, surpassing the effectiveness of immunization with cancer cells undergoing immunogenic cell death. Furthermore, induction of senescence in human primary cancer cells enhances their ability to activate autologous antigen-specific tumor-infiltrating CD8 lymphocytes. This study highlights the potential of exploiting senescent cancer cells to develop efficient and protective CD8-dependent antitumor immune responses.
Article
Multidisciplinary Sciences
Olga Boix, Marion Martinez, Santiago Vidal, Marta Gimenez-Alejandre, Lluis Palenzuela, Laura Lorenzo-Sanz, Laura Quevedo, Olivier Moscoso, Jorge Ruiz-Orera, Pilar Ximenez-Embun, Nikaoly Ciriaco, Paolo Nuciforo, Camille Stephan-Otto Attolini, M. Mar Alba, Javier Munoz, Tian V. Tian, Ignacio Varela, Ana Vivancos, Santiago Ramon Cajal, Purificacion Munoz, Carmen Rivas, Maria Abad
Summary: The human transcriptome contains small open reading frames (sORFs) that encode microproteins with largely unexplored functions. In this study, the authors show that TINCR lncRNA encodes a ubiquitin-like protein (UBL) called pTINCR, which is expressed in many epithelia and promotes epithelial differentiation through the SUMOylation and activation of CDC42. They also found that low expression of TINCR is associated with worse prognosis in several epithelial cancers.
NATURE COMMUNICATIONS
(2022)
Article
Developmental Biology
Cristina de Lope, Rebeca Garcia-Lucena, Marta Magarinos, Yolanda Leon, Nuria Casa-Rodriguez, Nuria Contreras, Carmen Escudero-Iriarte, Isabel Varela-Nieto, Pascal Maire, Ignacio Palmero
Summary: Developmental senescence, a type of programmed senescence, plays a role in embryonic morphogenesis. The SIX1 homeoprotein, known for its role in organogenesis, is also found to repress adult cellular senescence. Dysfunction of senescence may be connected to the developmental defects associated with SIX1 deficiency, as shown by studies on Six1-deficient mice. The aberrant senescence and altered morphogenesis in the inner ear of Six1-deficient mice suggests a link between senescence and disease through deregulation of the TGF beta/BMP pathway.
Article
Immunology
Daniel Alvarez-Sierra, Nerea Sanchez-Gaona, Maria Cruz Cobo, Alba Escriche, Maria Abad, Aroa Gomez-Brey, Irene Bello, Enric Caubet, Oscar Gonzalez, Carles Zafon, Carmela Iglesias, Pablo Moreno, Anna Petitj, Marco Antonio Fernandez-Sanmartin, Monica Martinez-Gallo, Ricardo Pujol-Borrell
Summary: Immune Checkpoint Receptors play a role in regulating immune responses and preventing tissue damage. Inhibiting the PD-1/PD-L1 receptor axis has shown promising results in cancer immunotherapy but can also lead to autoimmune adverse effects. This study investigates the role of PD-1/PD-L1 in the interaction between T cells and thyroid cells, and suggests that TFCs suppress T cell proliferation through the expansion of DN T cells, rather than PD-1/PD-L1. These findings contribute to our understanding of immune regulation and suggest alternative pathways for tumor evasion.
JOURNAL OF AUTOIMMUNITY
(2023)
Article
Oncology
Irene Carretero-Barrio, Tamara Caniego-Casas, Marta Rosas, Maria Concepcion Sanchez, Noelia Martinez-Janez, Miguel Chiva, David Sarrio, Gema Moreno-Bueno, Jose Palacios, Belen Perez-Mies
Summary: HER2-equivocal cases represent around 15% of breast carcinomas, and 20-40% of them are HER2-amplified. The evaluation of HER2 amplification status in equivocal cases is crucial for patient management. In this study, we investigated the performance of STRAT4, a RT-qPCR platform, compared to the recommended methods for the evaluation of HER2-equivocal cases. The results showed that STRAT4 is not reliable for the assessment of HER2 amplification status in equivocal cases.
Article
Cell Biology
Gracia Mendoza, Rebeca Gonzalez-Pastor, Juan Miguel Sanchez, Altamira Arce-Cerezo, Miguel Quintanilla, Gema Moreno-Bueno, Anna Pujol, Carolina Belmar-Lopez, Alba de Martino, Efren Riu, Tristan A. Rodriguez, Pilar Martin-Duque
Summary: The induction of pluripotency can be achieved by enforced expression of different gene combinations in somatic cells. A previous report showed that the adenoviral E1a gene can induce the expression of two Yamanaka factors and epigenetic changes. In this study, the over-expression of E1a-12S was found to be sufficient to induce pluripotent-like characteristics in mouse embryonic fibroblasts through the activation of the pluripotency gene regulatory network. These findings provide empirical evidence for partial reprogramming with a single factor and a potential mechanistic explanation for viral-induced neoplasia.
Article
Biochemistry & Molecular Biology
Mireia Pujals, Carla Mayans, Chiara Bellio, Olga Mendez, Emanuela Greco, Roberta Fasani, Merce Alemany-Chavarria, Esther Zamora, Laura Padilla, Francesc Mitjans, Paolo Nuciforo, Francesc Canals, Lara Nonell, Maria Abad, Cristina Saura, Josep Tabernero, Josep Villanueva
Summary: Epithelial/mesenchymal (E/M) plasticity is important in both embryogenesis and tumorigenesis. The role of receptor for advanced glycation end products (RAGE) in triple-negative breast cancer (TNBC) is unclear. This study shows that RAGE signaling maintains the mesenchymal phenotype of aggressive TNBC cells through the expression of SNAIL1 and its crosstalk with the TGF-β pathway. RAGE inhibition promotes epithelial features and reduces migration and invasion capacities. In vivo inhibition of RAGE reduces metastasis incidence and improves survival.
Article
Oncology
David Tamborero, Rodrigo Dienstmann, Maan Haj Rachid, Jorrit Boekel, Adria Lopez-Fernandez, Markus Jonsson, Ali Razzak, Irene Brana, Luigi De Petris, Jeffrey Yachnin, Richard D. Baird, Yohann Loriot, Christophe Massard, Patricia Martin-Romano, Frans Opdam, Richard F. Schlenk, Claudio Vernieri, Michele Masucci, Xenia Villalobos, Elena Chavarria, Judith Balmana, Giovanni Apolone, Carlos Caldas, Jonas Bergh, Ingemar Ernberg, Stefan Frohling, Elena Garralda, Claes Karlsson, Josep Tabernero, Emile Voest, Jordi Rodon, Janne Lehtio
Summary: This article presents the implementation of the Molecular Tumor Board Portal, a system that integrates and interprets genomics and clinical data to support clinical decision-making in precision oncology. The system automates the interpretation and reporting of sequencing results, reducing errors and promoting consistent decision-making and data capture. It also facilitates collaborative discussion through information-rich patient reports and interactive content.