Article
Biochemistry & Molecular Biology
Min Gyu Lee, Hwamok Oh, Jong Woo Park, Jueng Soo You, Jeung-Whan Han
Summary: Nuclear S6K1 functions in the regulation of Wnt target gene expression and has an impact on cell proliferation and invasion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Bei Tao, Yi Song, Yao Wu, Xiaobo Yang, Tangming Peng, Lilei Peng, Kaiguo Xia, Xiangguo Xia, Ligang Chen, Chuanhong Zhong
Summary: This study found that a stiffer matrix can promote the stemness of glioma cells by activating the BCL9L/Wnt/beta-catenin signaling pathway. Additionally, gigantol can enhance the effectiveness of traditional chemotherapy and radiotherapy by inhibiting Wnt/beta-catenin signaling, providing a potential strategy for clinical treatment of gliomas.
Article
Environmental Sciences
Bugao Guan, Jun Ma, Zhi Yang, Fei Yu, Jian Yao
Summary: The lncRNA NCK1-AS1 is highly expressed in gastric cancer and acts as an oncogene by competitively binding to miR-22-3p to upregulate BCL9 expression, leading to the activation of the Wnt/β-catenin signaling pathway and promoting gastric cancer progression.
ENVIRONMENTAL TOXICOLOGY
(2021)
Article
Chemistry, Medicinal
Zhen Wang, Min Zhang, Harriet M. Thompson, Haitao Ji
Summary: A series of new small-molecule beta-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction inhibitors were reported. Among them, compound 21 showed potent inhibition in cellular context and demonstrated higher potential in regulating transcription and expression of beta-catenin target genes and suppressing survival of beta-catenin-dependent cancer cells.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Chemistry, Medicinal
Hao Zhang, Ya Bao, Chenglong Liu, Jianqi Li, Di Zhu, Qingwei Zhang
Summary: The Wnt/β-catenin signaling pathway plays a crucial role in organism development and disease, making the direct targeting of protein-protein interactions a promising strategy for pathway inhibition. Despite the early stage of research in this area, there is hope for future development of inhibitors.
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Ruqing Gao, Xiaoqiang Zheng, Aimin Jiang, Wangxiao He, Tianya Liu
Summary: The tumor-specific biomimetic Wnt pathway suppressor CM-CA effectively inhibits the Wnt/β-catenin signaling pathway and cellular proliferation in lung adenocarcinoma, leading to significant tumor growth inhibition. CM-CA also promotes T cell infiltration and enhances the immune response within tumor tissues.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Gesa Richter, Tianshu Gui, Benjamin Bourgeois, Chintan N. Koyani, Peter Ulz, Ellen Heitzer, Dirk von Lewinski, Boudewijn M. T. Burgering, Ernst Malle, Tobias Madl
Summary: The research identified the Wnt signaling pathway as a key target of FOXP2-dependent transcriptional regulation, showing that beta-catenin plays a role in regulating FOXP2 transcriptional activity. The study used nuclear magnetic resonance spectroscopy to uncover the molecular details of the interactions between beta-catenin and FOXP2, demonstrating the importance of the FOXP2 alpha-helical motif in transcriptional regulation.
Article
Dentistry, Oral Surgery & Medicine
Jun Wang, Yong Jiang, Xudong Xie, Shiwen Zhang, Chunmei Xu, Yinghong Zhou, Jian Q. Feng
Summary: This study demonstrates that murine molar root elongation is precisely regulated by Wnt/beta-catenin signaling within a narrow window of time, from newborn to the 5th day. Activation of beta-catenin at different time points affects the extent of root elongation, indicating a high sensitivity of root elongation to changes in beta-catenin levels.
Article
Multidisciplinary Sciences
Abhishek Sinha, Vinson B. Fan, Aravinda-Bharathi Ramakrishnan, Nicole Engelhardt, Jennifer Kennell, Ken M. Cadigan
Summary: SOX9 promotes turnover of β-catenin independently of the destruction complex and proteasome in mammalian cell culture. This requires the activation of MAML2, which acts as a coactivator for SOX9 in antagonizing the Wnt/β-catenin pathway. This newly identified pathway provides a parallel mechanism for restricting Wnt/β-catenin signaling.
Article
Developmental Biology
Gianluca Zambanini, Anna Nordin, Mattias Jonasson, Pierfrancesco Pagella, Claudio Cantu
Summary: We developed a modified version of CUT&RUN called LoV-U, which allows for stable and reproducible generation of beta-catenin binding profiles, uncovering its direct target genes in human cells and mouse tissues. This method outperforms the original CUT&RUN when targeting co-factors that do not bind DNA, and is suitable for processing multiple samples simultaneously.
Article
Cell Biology
Ting Lei, Wenwu Zhang, Yongyin He, Shi Wei, Xiaoyu Song, Yi Zhu, Guoqing Luo, Zhenzhan Kuang, Guanjie Li, Quan Zhou, Zhaohui Sun, Bin Xiao, Linhai Li
Summary: Zinc finger protein 276 (ZNF276) is highly expressed in breast cancer and is associated with poor prognosis. It plays a crucial role in the proliferation, migration, and invasion of breast cancer cells both in vitro and in vivo. ZNF276 controls the expression of various growth and metastasis-related genes and promotes the activation of the Wnt/beta-catenin pathway. It interacts with MAGEB2 to enhance the regulation of CYP1B1, leading to increased cell proliferation and metastasis. Targeting the ZNF276/MAGEB2 axis may serve as a potential therapeutic strategy for breast cancer patients.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Samuel Trujano-Camacho, David Cantu-de Leon, Izamary Delgado-Waldo, Jossimar Coronel-Hernandez, Oliver Millan-Catalan, Daniel Hernandez-Sotelo, Cesar Lopez-Camarillo, Carlos Perez-Plasencia, Alma D. Campos-Parra
Summary: In cervical cancer patients, many genes of the Wnt/beta-catenin pathway are dysregulated, indicating the pathway's aberrant activation. In vitro experiments showed that the drug C59 efficiently inhibits the Wnt/beta-catenin pathway in CC cells.
FRONTIERS IN ONCOLOGY
(2021)
Review
Pharmacology & Pharmacy
Beibei Ni, Meijuan Sun, Jun Zhao, Jiao Wang, Zhanqi Cao
Summary: The Wnt/beta-catenin signaling pathway plays a crucial role in adult heart development and cardiac tissue homeostasis and is involved in various cardiac diseases. Understanding the role of this pathway in cardiac diseases is important for their treatment and diagnosis.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Rasha M. S. M. Mohamed, Enssaf Ahmad Ahmad, Bothina H. F. Omran, Amr T. Sakr, Islam A. A. E-H Ibrahim, Mona F. Mahmoud, Mostafa E. El-Naggar
Summary: This study investigated the role of a and 13-adrenergic receptors (13ARs) in the dexamethasone-induced nephrotoxicity and found that blocking either a1ARs or 13ARs can effectively protect against the nephrotoxicity. However, the combined blocking of a1ARs and 13ARs does not enhance the renal protective effects.
Article
Biochemistry & Molecular Biology
Mei-Jen Hsieh, Ching-Chieh Weng, Yu-Chun Lin, Chia-Chen Wu, Li-Tzong Chen, Kuang-Hung Cheng
Summary: This study revealed the importance of the Wnt/β-catenin signaling pathway in pancreatic cancer, showing that loss of LKB1 affects cystadenoma development and that the beta-catenin inhibitor FH535 can effectively suppress LKB1 loss-driven cystadenoma and slow down pancreatic cancer progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Cristina Fugazza, Gloria Barbarani, Sudharshan Elangovan, Maria Giuseppina Marini, Serena Giolitto, Isaura Font-Monclus, Maria Franca Marongiu, Laura Manunza, John Strouboulis, Claudio Cantu, Fabio Gasparri, Silvia M. L. Barabino, Yukio Nakamura, Sergio Ottolenghi, Paolo Moi, Antonella Ellena Ronchi
Summary: Coup-TFII is identified as a specific activator of the gamma-globin gene, playing a role in activating gamma-globin expression during early embryonic/fetal stages. Overexpression of Coup-TFII can overcome the repression of gamma-globin in adult cells, while knockout of Coup-TFII increases the beta/gamma+beta globin ratio.
Article
Multidisciplinary Sciences
David Buechel, Nami Sugiyama, Natalia Rubinstein, Meera Saxena, Ravi K. R. Kalathur, Fabiana Luond, Vida Vafaizadeh, Tomas Valenta, George Hausmann, Claudio Cantu, Konrad Basler, Gerhard Christofori
Summary: The transcriptional activity of beta-catenin plays a crucial role in the malignant progression of breast cancer, affecting tumor growth, invasion, and metastasis formation. This contrasts its adhesion function, highlighting the importance of Wnt/beta-catenin-dependent transcription in cancer progression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell & Tissue Engineering
Pierfrancesco Pagella, Laura de Vargas Roditi, Bernd Stadlinger, Andreas E. Moor, Thimios A. Mitsiadis
Summary: The Notch signaling pathway plays a crucial role in mediating interactions between perivascular stem cells and their niches in human dental mesenchymal tissues, influencing the response to traumatic injuries in vivo. These stem cells can be modulated by cues from the microenvironment, highlighting the pivotal importance of Notch signaling in tissue homeostasis and regeneration.
STEM CELLS TRANSLATIONAL MEDICINE
(2021)
Article
Cell Biology
Miriam Pagin, Mattias Pernebrink, Mattia Pitasi, Federica Malighetti, Chew-Yee Ngan, Sergio Ottolenghi, Giulio Pavesi, Claudio Cantu, Silvia K. Nicolis
Summary: The transcription factor SOX2 is crucial for brain development and neural stem cell maintenance. Study shows that FOS, a SOX2 transcriptional target, can rescue defects in neuronal production caused by Sox2 deletion.
Article
Cell Biology
Chai Foong Lai, Juliet Shen, Anamaria Balic, Pierfrancesco Pagella, Martin E. Schwab, Thimios A. Mitsiadis
Summary: The study identified the widespread distribution of Nogo-A in human teeth, and clarified its significant regulatory role in the development of dental pulp stem cells, indicating its potential application in clinics.
Article
Multidisciplinary Sciences
Thimios A. Mitsiadis, Lucia -Rojo, Anamaria Balic, Silvio Weber, Paul Saftig, Pierfrancesco Pagella
Summary: The Adam10/Notch axis controls dental epithelial cell boundaries, cell fate switch, and proper enamel formation in continuously growing incisors.
Article
Biochemistry & Molecular Biology
Thimios A. Mitsiadis, Pierfrancesco Pagella, Terence D. Capellini, Moya Meredith Smith
Summary: The Notch pathway is involved in cell fate specification and embryonic development. The Jagged2 gene, which encodes a ligand for Notch receptors, is expressed early in tooth development. Mutations in Jagged2 result in abnormal tooth morphology and impaired enamel deposition. The Notch signaling cascade is disrupted in Jagged2 mutant teeth, leading to dental structures more reminiscent of fish enamel. We propose that the increased number of Notch homologues in metazoa enabled the formation and maintenance of distinctive cell fates within organs and tissues during evolution.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lovisa Oerkenby, Signe Skog, Helen Ekman, Alessandro Gozzo, Unn Kugelberg, Rashmi Ramesh, Srivathsa Magadi, Gianluca Zambanini, Anna Nordin, Claudio Cantu, Daniel Naett, Anita Oest
Summary: Early-life stress can lead to long-term effects on adult health and disease risk, and this study reveals that these effects can be initiated in Drosophila embryos before the main wave of zygotic transcription. The researchers found that a short heat shock in early embryos resulted in changes in maternal miRNA and the expression of certain genes. They propose that maternal miRNAs, retained in response to an early embryonic heat shock, play a role in shaping the establishment of heterochromatin during early development.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Oncology
Toshiyasu Suzuki, Anna Kilbey, Nuria Casa-Rodriguez, Amy Lawlor, Anastasia Georgakopoulou, Hannah Hayman, Kyi Lai Yin Swe, Anna Nordin, Claudio Cantu, Pierre Vantourout, Rachel A. Ridgway, Ryan M. Byrne, Lei Chen, Michael P. Verzi, David M. Gay, Ester Gil Vazquez, Hayley L. Belnoue-Davis, Kathryn Gilroy, Anne Helene Kostner, Christian Kersten, Chanitra Thuwajit, Ditte K. Andersen, Robert Wiesheu, Anett Jandke, Karen Blyth, Antonia K. Roseweir, Simon J. Leedham, Philip D. Dunne, Joanne Edwards, Adrian Hayday, Owen J. Sansom, Seth B. Coffelt
Summary: Colon cancer cells evade immune surveillance by suppressing the expression of y8 T cells and Butyrophilin-like (BTNL) molecules. Reexpression of BTNL enhances the survival and activation of y8 T cells, but it does not affect their cancer-killing ability or recruitment to orthotopic tumors. However, inhibition of 13-catenin signaling through genetic deletion of Bcl9/Bcl9L restores the expression of Hnf4a, Hnf4g, and Btnl genes as well as infiltration of y8 T cells into tumors.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Cell Biology
Thimios A. Mitsiadis, Pierfrancesco Pagella, Helder Gomes Rodrigues, Alexander Tsouknidas, Liza L. Ramenzoni, Freddy Radtke, Albert Mehl, Laurent Viriot
Summary: Evolutionary changes in vertebrates are often accompanied by genetic alterations that affect tooth crown shape. The Notch pathway, a highly conserved signaling pathway, plays a crucial role in morphogenetic processes, including tooth development. Experimental studies on developing mouse molars showed that the loss of the Notch-ligand Jagged1 leads to minor modifications in tooth crown shape, similar to those observed during the evolution of Muridae species. RNA sequencing analysis revealed that these alterations are caused by changes in the expression of over 2000 genes, and that Notch signaling interacts with other important morphogenetic networks, such as Wnts and Fibroblast Growth Factors. The findings from this study provide insights into the role of Notch/Jagged1-mediated signaling in dental variations during evolution.
Article
Oncology
Simon Soderholm, Amaia Jauregi-Miguel, Pierfrancesco Pagella, Valeria Ghezzi, Gianluca Zambanini, Anna Nordin, Claudio Cantu
Summary: Wnt signaling activates the nuclear translocation of beta-catenin, which interacts with DNA-bound TCF/LEF transcription factors to regulate target gene specificity. However, the expression patterns of Wnt target genes do not always overlap. In this study, single-cell analysis revealed heterogeneity in the activation of Wnt target genes in human embryonic stem cells and other Wnt-responding cell types. The uncoupling of Wnt target gene expression suggests the presence of additional mechanisms that contribute to the diverse transcriptional outputs mediated by Wnt/beta-catenin signaling in single cells.
EXPERIMENTAL CELL RESEARCH
(2023)
Article
Biotechnology & Applied Microbiology
Anna Nordin, Gianluca Zambanini, Pierfrancesco Pagella, Claudio Cantu
Summary: CUT & RUN is a technique for mapping genome-wide binding profiles, but its unique biochemistry and data analysis methods result in undesired high-signal regions. This study analyzes CUT & RUN data from human and mouse genomes and finds that these problematic regions persist even after applying negative control and ENCODE blacklist removal. Experimental validation shows that these regions capture over 80% of the identified peaks. Therefore, removing these problematic regions is recommended to improve the reliability of CUT & RUN data.
Article
Dentistry, Oral Surgery & Medicine
Anamaria Balic, Dilara Perver, Pierfrancesco Pagella, Hubert Rehrauer, Bernd Stadlinger, Andreas E. Moor, Viola Vogel, Thimios A. Mitsiadis
Summary: In this study, a comprehensive single-cell atlas of carious human teeth was generated using single-cell RNA sequencing analysis and immunostaining. The study found modifications in various cell clusters within the carious dental pulp, including immune cells, mesenchymal stem cells, and fibroblasts. These modifications led to an increase in extracellular matrix components and myofibroblast enrichment. The study also revealed molecular, cellular, and biomechanical alterations in the carious dental pulp, indicative of extensive extracellular matrix remodeling.
INTERNATIONAL JOURNAL OF ORAL SCIENCE
(2023)
Article
Cell & Tissue Engineering
P. Pagella, A. Cordiale, G. D. Marconi, O. Trubiani, M. Rasponi, T. A. Mitsiadis
Summary: Various factors contribute to dental pathologies, and current clinical approaches using inert materials for tooth restoration do not fully restore physiological function. Although there have been attempts to use dental mesenchymal stem cells for tooth tissue regeneration, the lack of suitable platforms that mimic the complexity of human dental tissues has hindered clinical applications. Efforts have been made to develop innovative systems for in vitro modeling of human tooth physiology.
EUROPEAN CELLS & MATERIALS
(2021)
Article
Cell & Tissue Engineering
Miriam Pagin, Mattias Pernebrink, Simone Giubbolini, Cristiana Barone, Gaia Sambruni, Yanfen Zhu, Matteo Chiara, Sergio Ottolenghi, Giulio Pavesi, Chia-Lin Wei, Claudio Cantu, Silvia K. Nicolis
Summary: The Sox2 transcription factor is crucial for the long-term self-renewal of neural stem cells. The downstream molecule Fos plays a key role in maintaining cell proliferation, possibly through regulating the expression of Socs3. The findings suggest a network of interactions involving Sox2, Fos, and Socs3 in regulating NSC proliferation and maintenance.
