Article
Multidisciplinary Sciences
Tobias Troost, Udi Binshtok, David Sprinzak, Thomas Klein
Summary: The selection of a single sensory organ precursor (SOP) from a large group of cells in Drosophila is controlled by cis-inhibition (CI), where the ligand Delta inhibits the Notch receptor in the same cell. The mammalian ligand Dl-like 1 does not exhibit cis-inhibition in Drosophila. A mathematical model and experiments show that Mindbomb1 induces basal Notch activity, which is suppressed by CI, highlighting the trade-off between basal Notch activity and CI for SOP selection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Rheumatology
Yvonne L. Bartels, Peter L. E. M. van Lent, Peter M. van der Kraan, Arjen B. Blom, Kimberly M. Bonger, Martijn H. J. van den Bosch
Summary: Local and systemic low-grade inflammation, particularly involving the innate immune system, plays a significant role in the development of osteoarthritis (OA). Toll-like receptor 4 (TLR4) is a crucial receptor responsible for initiating this inflammatory response. Various ligands for TLR4, including damage-associated molecular patterns (DAMPs), can activate TLR4 signaling in the joint, resulting in the production of pro-inflammatory and catabolic mediators that contribute to joint damage. This review discusses the role of TLR4 ligands and signaling in OA, as well as different methods to inhibit TLR4 signaling and their potential applications and challenges in dampening inflammation in OA.
Article
Oncology
Xianning Lai, Sarah Kit Leng Lui, Hiu Yan Lam, Yuta Adachi, Wen Jing Sim, Natali Vasilevski, Nicola J. Armstrong, Stephanie Claire Bridgeman, Nathan Michael Main, Tuan Zea Tan, Janina E. E. Tirnitz-Parker, Jean Paul Thiery, Hiromichi Ebi, Alan Prem Kumar, Pieter Johan Adam Eichhorn
Summary: Despite limited overall responses of SHP2 inhibitors in RAS-dependent tumors, this study identifies SHP2 as a critical regulator of TGF beta activity and demonstrates its impact on migration, senescence, and cell survival. Combining SHP2 and TGF beta inhibitors may enhance tumor responses and improve patient outcomes.
NPJ PRECISION ONCOLOGY
(2023)
Article
Hematology
Helal Mohammed Mohammed Ahmed, Subbaiah Chary Nimmagadda, Yahya S. Al-Matary, Maren Fiori, Tobias May, Daria Frank, Pradeep Kumar Patnana, Christian Recher, Christoph Schliemann, Jan-Henrik Mikesch, Thorsten Koenig, Frank Rosenbauer, Wolfgang Hartmann, Jan Tuckermann, Ulrich Duhrsen, Wei Lanying, Martin Dugas, Bertram Opalka, Georg Lenz, Cyrus Khandanpour
Summary: This study showed functional differences between AML MSCs and HD MSCs, with Notch signaling in AML MSCs enhancing AML cell proliferation, while dexamethasone or Notch inhibitors could disrupt the interaction between AML cells and AML MSCs, improving treatment outcomes in AML patients.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Joanna Kalafut, Arkadiusz Czerwonka, Karolina Czapla, Alicja Przybyszewska-Podstawka, Justyna Magdalena Hermanowicz, Adolfo Rivero-Muller, Lidia Borkiewicz
Summary: Notch1 signaling plays a diverse role in tissue development and homeostasis. The relationship between NOTCH1 expression and the development of health disorders, especially cancers, is intensively studied. Control of Notch1 signaling involves not only transcriptional regulation but also various post-translational events, including ligand-dependent mechanical activation and interaction with other signaling molecules, such as long non-coding RNAs (lncRNAs).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Mauricio T. Nascimento, Monica Franca, Augusto M. Carvalho, Camila F. Amorim, Fabio Peixoto, Daniel Beiting, Phillip Scott, Edgar M. Carvalho, Lucas P. Carvalho
Summary: The study found that Notch signaling can protect against pathologic inflammatory response in CL patients, and a specific gamma-secretase inhibitor JLK6 can reduce the in-vitro inflammatory response, potentially serving as an adjuvant treatment for CL patients.
EMERGING MICROBES & INFECTIONS
(2021)
Article
Medicine, General & Internal
Lisanne Mout, Martin E. van Royen, Corrina de Ridder, Debra Stuurman, Wesley S. van de Geer, Rute Marques, Stefan A. J. Buck, Pim J. French, Harmen J. G. van de Werken, Ron H. J. Mathijssen, Ronald de Wit, Martijn P. Lolkema, Wytske M van Weerden
Summary: The study demonstrated that combining enzalutamide with cabazitaxel significantly enhanced the anti-tumor activity of cabazitaxel in CRPC models. Enzalutamide alone did not reduce tumor growth effectively, but it suppressed AR signaling significantly.
Article
Environmental Sciences
Yong Wang, Wen Li, Fangmei Huang, Xiaojian Wu, Wenbin Chen, Ming Dong, Jie Zhou
Summary: The study demonstrates that SCA inhibits the proliferation of myeloma cells by promoting pro-apoptotic proteins and targeting the expression of Notch3. This suggests that SCA may have potential for further development as a treatment for multiple myeloma.
ENVIRONMENTAL TOXICOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Torcato Martins, Yao Meng, Boguslawa Korona, Richard Suckling, Steven Johnson, Penny A. Handford, Susan M. Lea, Sarah J. Bray
Summary: Accurate Notch signalling is crucial for development and homeostasis, with recent studies showing the importance of the conserved N-terminal C2 domain in Notch ligands. Mutations in the beta 1-2 loop of the Delta C2 domain affect phospholipid binding and compromise ligand function in vivo. These findings highlight the essential role of C2 domain phospholipid binding in fine-tuning the balance of trans and cis ligand-receptor interactions for robust signalling.
Review
Cell Biology
Guihong Liu, Tao Chen, Zhenyu Ding, Yang Wang, Yuquan Wei, Xiawei Wei
Summary: The FGF-FGFR signaling pathway and the VEGF-VEGFR signaling pathway play important roles in the treatment of tumors, and inhibitors targeting these two pathways can optimize therapeutic effects and expand the antitumor range. In addition, biomarkers should be developed in the future to predict efficacy, and combination with immune checkpoint inhibitors is a promising direction.
CELL PROLIFERATION
(2021)
Article
Cell Biology
Ting Hao, Rui Zhang, Tian Zhao, Juan Wu, Wai Keung Leung, Jie Yang, Weibin Sun
Summary: P. gingivalis may promote inflammatory responses in periodontitis by inhibiting the AhR signaling pathway.
CELL PROLIFERATION
(2023)
Article
Pharmacology & Pharmacy
Chih-Chin Shih, Melissa Chan, Nicholas S. Kirkby, Ivana Vojnovic, Jane A. Mitchell, Paul C. Armstrong, Timothy D. Warner
Summary: The study demonstrates a synergistic relationship between P2Y(12) receptor antagonists and adenosine signaling, with their efficacy partly dependent on the presence of endogenous adenosine. Despite reported differences in their effects upon adenosine reuptake, both prasugrel and ticagrelor show similar synergistic effects on platelet inhibition in the presence of adenosine or NECA.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemical Research Methods
Daipeng M. Chen, Zary Forghany, Xinxin M. Liu, Haijiang Wang, Roeland M. H. M. Merks, David Baker
Summary: In this study, a new model of Notch signaling is proposed, in which ligand monomers promote Notch receptor transactivation and ligand dimers induce cis inhibition. This model provides a concrete molecular distinction between the main branches of Notch signaling and successfully recapitulates experimental results. It offers a novel perspective for understanding Notch-regulated biological processes.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Ansarullah, Chirag Jain, Fataneh Fathi Far, Sarah Homberg, Katharina Wissmiller, Felizitas Grafin von Hahn, Aurelia Raducanu, Silvia Schirge, Michael Sterr, Sara Bilekova, Johanna Siehler, Julius Wiener, Lena Oppenlaender, Amir Morshedi, Aimee Bastidas-Ponce, Gustav Collden, Martin Irmler, Johannes Beckers, Annette Feuchtinger, Michal Grzybek, Christin Ahlbrecht, Regina Feederle, Oliver Plettenburg, Timo D. Mueller, Matthias Meier, Matthias H. Tschoep, Uenal Coskun, Heiko Lickert
Summary: The discovery of inceptor, an inhibitor of insulin receptor (INSR) and IGF1 receptor (IGF1R) signalling in mouse beta-cells, sheds light on a potential molecular target for INSR-IGF1R sensitization and diabetes therapy. The study shows that inceptor plays a role in shielding insulin-producing beta-cells from constitutive pathway activation, which could have implications for improving glucose tolerance in vivo.
Article
Oncology
Liliana Ordonez, Giusy Tornillo, Howard Kendrick, Trevor Hay, Matthew John Smalley
Summary: The interaction between NOTCH and PI3K/AKT signaling pathways determines the development and type of mammary tumors in mice.
