Review
Oncology
Siwei Yu, Ruyue Han, Runliang Gan
Summary: This review aims to analyze the mechanisms of action of related molecules in the Wnt/beta-catenin pathway in hematologic malignancies and explore their feasibility as therapeutic targets.
BIOMARKER RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Mathilde Cadoux, Stefano Caruso, Sandrine Pham, Angelique Gougelet, Celine Pophillat, Rozenn Riou, Robin Loesch, Sabine Colnot, Cong Trung Nguyen, Julien Calderaro, Severine Celton-Morizur, Nadia Guerra, Jessica Zucman-Rossi, Chantal Desdouets, Jean-Pierre Couty
Summary: The expression of NKG2D ligands is associated with aggressive liver tumorigenesis, and downregulation of these ligands by beta-catenin signaling may contribute to the less aggressive phenotype of CTNNB1-mutated HCC tumors.
JOURNAL OF HEPATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Janson Tse, Ryan O'Keefe, Angela Rigopolous, Annalisa L. E. Carli, Jo Waaler, Stefan Krauss, Matthias Ernst, Michael Buchert
Summary: Specific signalling thresholds of the WNT/beta-catenin pathway affect embryogenesis and tissue homeostasis. Currently, there is a lack of specific in vivo assays to evaluate inhibitors of WNT/beta-catenin signalling. We present a simple in vivo assay to assess the efficacy and bioavailability of candidate compounds.
Article
Cell & Tissue Engineering
Kai Hang, Li Ying, Jinwu Bai, Yibo Wang, Zhihui Kuang, Deting Xue, Zhijun Pan
Summary: The study showed that the silencing of SERPINB2 can promote osteogenic differentiation of BMSCs through the Wnt/β-catenin signaling pathway. In vivo experiments demonstrated that silencing SERPINB2 effectively improves bone fracture healing, suggesting that SERPINB2 may be a novel target for bone fracture healing.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Pathology
Zhenyou Feng, Huiming Ding, Zhiwei Peng, Kongwang Hu
Summary: This study investigated the relationship between KDM6A expression and patient prognosis, as well as the role of KDM6A in GC development. Immunohistochemical analysis of 107 GC patients' tumors revealed that reduced KDM6A expression was associated with shorter survival time. In vitro tests showed that KDM6A gene suppression inhibited GC cell proliferation, migration, and invasion, while high KDM6A expression promoted these processes. The study also found that KDM6A down-regulation affected the expression of various proteins involved in Wnt/beta-catenin signaling and EMT, and blocking this pathway reversed the aggressive behavior of low KDM6A-expressing GC cells.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Review
Cell Biology
Sandy Winfield Jere, Heidi Abrahamse, Nicolette Nadene Houreld
Summary: Cell signalling plays a crucial role in wound healing, and dysregulation of signalling pathways can lead to chronic wounds. The interaction between the AKT and beta-catenin signalling pathways influences diabetic wound healing, and photobiomodulation can enhance this process.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)
Article
Biotechnology & Applied Microbiology
Chaoqun Dong, Zhigang Wang, Peng Shen, Yingguo Chen, Jinshu Wang, Hongbo Wang
Summary: Epigallocatechin-3-gallate (EGCG), a unique catechin from tea leaves, has potential anticancer effects in osteosarcoma. Cellular and animal experiments have shown that EGCG promotes apoptosis and inhibits proliferation, migration, and invasion of osteosarcoma cells. EGCG also suppresses tumor cell damage to bone and distant lung metastasis.
Article
Biochemistry & Molecular Biology
Joo Mi Yi, Tae-Hong Kang, Yu Kyeong Han, Ha Young Park, Ju Hwan Yang, Jin-Han Bae, Jung-Soo Suh, Tae-Jin Kim, Joong-Gook Kim, Yan-Hong Cui, Hiromu Suzuki, Kohei Kumegawa, Sung Joo Kim, Yi Zhao, In Ja Park, Seung-Mo Hong, Joon-Yong Chung, Su-Jae Lee
Summary: This study identifies Neuralized (NEURL) as a novel tumor suppressor gene that targets oncogenic Wnt/beta-catenin signaling in human cancers. NEURL expression is epigenetically regulated and suppressed in colorectal cancer. NEURL acts as an E3 ubiquitin ligase, interacting with oncogenic beta-catenin and reducing its cytoplasmic levels, thereby disrupting the canonical Wnt/beta-catenin pathway.
Review
Cell Biology
Gemma Sutton, Robert N. Kelsh, Steffen Scholpp
Summary: The neural crest (NC) is a multipotent cell population in vertebrate embryos with extraordinary migratory capacity, crucial for vertebrate development. The ongoing role of the Wnt/beta-catenin signalling pathway during NC development, especially in the induction of NC and specification of melanocytes, is discussed. Current understanding shows the continual involvement of Wnt/beta-catenin signalling in activating and maintaining the gene regulatory network during NC induction and pigment cell specification, with implications for emerging models and hypotheses on NC fate restriction.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Beatriz Martin-Carro, Julia Martin-Virgala, Sara Fernandez-Villabrille, Alejandra Fernandez-Fernandez, Marcos Perez-Basterrechea, Juan F. Navarro-Gonzalez, Javier Donate-Correa, Carmen Mora-Fernandez, Adriana S. Dusso, Natalia Carrillo-Lopez, Sara Panizo, Manuel Naves-Diaz, Jose L. Fernandez-Martin, Jorge B. Cannata-Andia, Cristina Alonso-Montes
Summary: Fibrosis plays a crucial role in the development of diabetic complications and dysfunction in the heart and kidneys. This study investigated the involvement of soluble Klotho, advanced glycation end products/receptor for AGEs, fibrotic Wnt/beta-catenin pathway, and pro-fibrotic pathways in the kidney and heart of diabetic rats. The findings suggested that diabetic rats had elevated levels of urinary sKlotho, AGEs, and sRAGE, and decreased levels of serum sKlotho. Fibrosis and RAGE levels were higher in the heart of diabetic rats compared to controls. The increase in sKlotho and sRAGE excretion may be due to polyuria in diabetic rats.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Chang Xu, Yu-han Ding, Kun Wang, Mengdi Hao, Huimin Li, Lei Ding
Summary: The study demonstrates that Cldn7 deficiency in CRC promotes stemness properties through Sox9-mediated Wnt/beta -catenin signaling. This finding elucidates the inhibitory role of Cldn7 in CRC and reveals a potential molecular mechanism, contributing to further research on Cldn7 and cancer stem cells.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Fisheries
Shuang Zhang, Shubing Fang, Shougang Song, Yudong Zheng, Beiping Tan, Lili Shi
Summary: The study found that modulating the activity of Wnt/beta-catenin signaling in Litopenaeus vannamei can affect growth performance and immunity, possibly through metabolic alterations. This highlights the potential for using immunostimulants in aquaculture.
AQUACULTURE REPORTS
(2021)
Article
Multidisciplinary Sciences
Prem Swaroop Yadav, Shuhao Feng, Qian Cong, Hanjun Kim, Yuchen Liu, Yingzi Yang
Summary: Job syndrome is a rare genetic disorder characterized by immune dysfunction and skeletal developmental abnormalities. Current treatment options are limited, but enhancing Wnt/β-catenin signaling could potentially reduce bone symptoms in patients with Job syndrome.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pharmacology & Pharmacy
Sapna Sayed, Jiaxing Song, Ling Wang, Tobias Achu Muluh, Boxin Liu, Zhixian Lin, Yun Tang, Zijie Su, Huan Li, Vivian Weiwen Xue, Shanshan Liu, Xianxiong Chen, Guangqian Zhou, Qi Sun, Desheng Lu
Summary: In this study, ISX9 was identified as a novel agonist of the Wnt/beta-catenin pathway, which activates hair regrowth and may be a potential treatment for alopecia.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Yeong Chan Ryu, Dong-Hwan Lee, Jiyong Shim, Jiyeon Park, You-Rin Kim, Sehee Choi, Soon Sun Bak, Young Kwan Sung, Soung-Hoon Lee, Kang-Yell Choi
Summary: KY19382 is identified as a drug that activates Wnt/beta-catenin signaling, promoting hair regeneration and growth with significant effects on DP cells, and demonstrating hair regrowth abilities in mouse models.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Sonia Azeggagh, Daniel C. Berwick
Summary: Current therapeutic approaches for Parkinson's disease focus on symptom relief rather than disease progression. Inhibition of LRRK2 function is a promising strategy due to its role in familial and idiopathic Parkinson's disease. Progress has been made in finding effective LRRK2 inhibitors, but the complexity of LRRK2 presents challenges and opportunities for unintended consequences. Multiple molecules are in clinical trials, providing cause for optimism in the search for alternative treatment options.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Clement Danis, Elian Dupre, Orgeta Zejneli, Raphaelle Caillierez, Alexis Arrial, Severine Begard, Justine Mortelecque, Sabiha Eddarkaoui, Anne Loyens, Francois-Xavier Cantrelle, Xavier Hanoulle, Jean-Christophe Rain, Morvane Colin, Luc Buee, Isabelle Landrieu
Summary: The study demonstrates the effectiveness of VHH Z70 in inhibiting Tau aggregation and reducing pathological Tau accumulation in brain neurons. By specifically targeting Tau within cells, VHH Z70 provides an immunological tool for targeting the intra-cellular compartment in tauopathies.
Article
Multidisciplinary Sciences
Pengli Zheng, Christopher J. Obara, Ewa Szczesna, Jonathon Nixon-Abell, Kishore K. Mahalingan, Antonina Roll-Mecak, Jennifer Lippincott-Schwartz, Craig Blackstone
Summary: This study demonstrates that three membrane-bound endoplasmic reticulum proteins interact preferentially with different microtubule populations, influencing organelle positioning and distribution in cells.
Article
Biochemistry & Molecular Biology
Peng-Peng Zhu, Hui-Fang Hung, Natalia Batchenkova, Jonathon Nixon-Abell, James Henderson, Pengli Zheng, Benoit Renvoise, Song Pang, C. Shan Xu, Stephan Saalfeld, Jan Funke, Yuxiang Xie, Fabian Svara, Harald F. Hess, Craig Blackstone
Summary: Researchers have generated an early onset rodent model of hereditary spastic paraplegia (HSP), which displays reliable behavioral and cellular readouts for testing novel therapies. The study reveals that in this model, the morphology of the endoplasmic reticulum (ER) undergoes changes that are linked to alterations in mitochondrial morphology and cytoskeletal organization.
HUMAN MOLECULAR GENETICS
(2022)
Correction
Multidisciplinary Sciences
Pengli Zheng, Christopher J. Obara, Ewa Szczesna, Jonathon Nixon-Abell, Kishore K. Mahalingan, Antonina Roll-Mecak, Jennifer Lippincott-Schwartz, Craig Blackstone
Article
Multidisciplinary Sciences
Joseph E. Chambers, Nikita Zubkov, Marketa Kubankova, Jonathon Nixon-Abell, Ioanna Mela, Susana Abreu, Max Schwiening, Giulia Lavarda, Ismael Lopez-Duarte, Jennifer A. Dickens, Tomas Torres, Clemens F. Kaminski, Liam J. Holt, Edward Avezov, James A. Huntington, Peter St George-Hyslop, Marina K. Kuimova, Stefan J. Marciniak
Summary: This study investigates the mechanism of protein misfolding in alpha(1)-antitrypsin deficiency, leading to cirrhosis. The researchers find that alpha(1)-antitrypsin polymers undergo a phase transition, forming a protein matrix that hinders the mobility of ER proteins. This phase transition is promoted by ER stress and facilitated by the ER chaperone calreticulin. The study also reveals that immobilization of ER chaperones within the polymer matrix contributes to ER dysfunction. These findings provide insights into proteinopathies and suggest ER chaperones as potential therapeutic targets.
Correction
Multidisciplinary Sciences
Anny Devoy, Georgia Price, Francesca De Giorgio, Rosie Bunton-Stasyshyn, David Thompson, Samanta Gasco, Alasdair Allan, Gemma F. Codner, Remya R. Nair, Charlotte Tibbit, Ross McLeod, Zeinab Ali, Judith Noda, Alessandro Marrero-Gagliardi, Jose M. Brito-Armas, Muhammet M. Ozturk, Michelle Simon, Edward O'Neill, Sam Bryce-Smith, Jackie Harrison, Gemma Atkins, Silvia Corrochano, Michelle Stewart, Lydia Teboul, Abraham Acevedo-Arozena, Elizabeth M. C. Fisher, Thomas J. Cunningham
Article
Neurosciences
Paige Mumford, Justin Tosh, Silvia Anderle, Eleni Gkanatsiou Wikberg, Gloria Lau, Sue Noy, Karen Cleverley, Takashi Saito, Takaomi C. Saido, Eugene Yu, Gunnar Brinkmalm, Erik Portelius, Kaj Blennow, Henrik Zetterberg, Victor Tybulewicz, Elizabeth M. C. Fisher, Frances K. Wiseman
Summary: This study found that in individuals with Down syndrome (DS), early onset Alzheimer's disease (AD) is associated with multiple copies of the APP gene on chromosome 21, while three copies of other genes on chromosome 21 can partially alleviate the accumulation of AP in the brain. This provides critical mechanistic insight into disease development and explains the typically later age of onset of dementia in DS individuals compared to those with familial AD caused by triplication of APP.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Adamantios Mamais, Alice Kaganovich, Kirsten Harvey
Summary: Recent progress in molecular biology and genetics has advanced our understanding of the pathogenesis of Parkinson's disease (PD), highlighting synergistic relationships with inflammatory and age-related processes. Genetic risk variants and inflammation play important roles in the development of PD, and there is an overlap between genes associated with increased risk for PD and autoimmune diseases. The pathogenesis of genetic PD is related to inflammatory signaling pathways.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Norbert Volkmar, Christian M. Gawden-Bone, James C. Williamson, Jonathon Nixon-Abell, James A. West, Peter H. St George-Hyslop, Arthur Kaser, Paul J. Lehner
Summary: The regulation of membrane lipid composition plays a crucial role in maintaining cellular homeostasis. This study identifies proteins that differ between mammalian cells fed saturated and unsaturated fatty acids, and reveals the role of the E3 ubiquitin ligase RNF145 and lipid hydrolase ADIPOR2 in membrane lipid composition sensing and regulation. The findings provide insights into a novel autoregulatory pathway that controls cellular membrane lipid homeostasis and prevents lipotoxic stress.
Article
Developmental Biology
Yushi Redhead, Dorota Gibbins, Eva Lana-Elola, Sheona Watson-Scales, Lisa Dobson, Matthias Krause, Karen J. Liu, Elizabeth M. C. Fisher, Jeremy B. A. Green, Victor L. J. Tybulewicz
Summary: Down syndrome (DS) is a common human chromosomal abnormality that leads to various phenotypic features, including craniofacial dysmorphology. Through analysis of a DS mouse model and genetic mapping, it was found that four regions on mouse chromosome 16, which correspond to Hsa21 in humans, contain dosage-sensitive genes that contribute to DS craniofacial abnormalities, with Dyrk1a identified as one of the causative genes. The study revealed that the earliest and most severe defects in the DS mouse skulls occur in bones of neural crest origin, and that abnormal mineralization of the skull base synchondroses is present. Additionally, increased dosage of Dyrk1a was found to result in decreased proliferation of neural crest cells and a reduction in size and cellularity of the frontal bone primordia.
Article
Cell Biology
Kourtney Sloan, Jared Thomas, Matthew Blackwell, Deanna Voisard, Eva Lana-Elola, Sheona Watson-Scales, Daniel L. Roper, Joseph M. Wallace, Elizabeth M. C. Fisher, Victor L. J. Tybulewicz, Randall J. Roper
Summary: This study investigates the effects of triplicated genes on mouse skeletal phenotypes and finds that they can both improve and worsen bone deficits.
DISEASE MODELS & MECHANISMS
(2023)
Review
Neurosciences
Elizabeth M. C. Fisher, Linda Greensmith, Andrea Malaspina, Pietro Fratta, Michael G. Hanna, Giampietro Schiavo, Adrian M. Isaacs, Richard W. Orrell, Thomas J. Cunningham, Abraham Acevedo Arozena
Summary: Amyotrophic lateral sclerosis (ALS) is a complex disorder with mostly unknown cause, but around 10% of cases are familial and caused by mutations in over 30 different genes. Mouse models exist for many genetic forms of ALS, but there is currently no model for the majority of ALS cases that are sporadic. The development of potential therapies has primarily relied on limited mouse models and has been tested on patients with different etiologies. The use of complex mouse models and patient stratification in clinical trials has proven successful in cancer research, and adopting a similar approach could lead to better understanding of ALS pathologies and faster translation of research findings into effective therapies.
MOLECULAR NEURODEGENERATION
(2023)
Article
Multidisciplinary Sciences
Nadia A. Erkamp, Tomas Sneideris, Hannes Ausserwoger, Daoyuan Qian, Seema Qamar, Jonathon Nixon-Abell, Peter St George-Hyslop, Jeremy D. Schmit, David A. Weitz, Tuomas P. J. Knowles
Summary: In this study, the authors investigate how biomolecular condensates can form an internal structure with dilute phase droplets via kinetic driving forces. The formation of biomolecular condensates through phase separation from proteins and nucleic acids is widely used by cells as a spatial organizational principle. This study demonstrates that complex internal architecture of condensates can arise from kinetic driving forces, providing insights into understanding and controlling the structure of condensates in vitro and in vivo.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Romain F. Laine, Hannah S. Heil, Simao Coelho, Jonathon Nixon-Abell, Angelique Jimenez, Theresa Wiesner, Damian Martinez, Tommaso Galgani, Louise Regnier, Aki Stubb, Gautier Follain, Samantha Webster, Jesse Goyette, Aurelien Dauphin, Audrey Salles, Sian Culley, Guillaume Jacquemet, Bassam Hajj, Christophe Leterrier, Ricardo Henriques
Summary: This article presents an enhanced super-resolution radial fluctuations (eSRRF) method that improves image fidelity and resolution. The method incorporates automated parameter optimization and has been validated across various imaging modalities and biological systems. Additionally, eSRRF has been extended to three dimensions by combining it with multifocus microscopy, enabling live-cell volumetric super-resolution imaging.
