Review
Oncology
Stefan Koch
Summary: This article discusses the control of the Wnt pathway by FOX proteins, and the contribution of their interaction to cancer initiation and progression. Further research on FOX biology may lead to new targeted treatments for cancer.
Article
Biochemistry & Molecular Biology
Zhaobo Cheng, Renjie Yu, Li Li, Junhao Mu, Yijia Gong, Fan Wu, Yujia Liu, Xiangyi Zhou, Xiaohua Zeng, Yongzhong Wu, Ran Sun, Tingxiu Xiang
Summary: In our research, we identified ZNF334 as a novel tumor suppressor of triple-negative breast cancer (TNBC). ZNF334 expression was usually reduced in breast cancer tissues and TNBC cell lines, likely due to promoter hypermethylation. Ectopic expression of ZNF334 suppressed the growth and metastatic capacity of TNBC cell lines, induced cell cycle arrest at S phase and apoptosis. Additionally, re-expression of ZNF334 restored the Epithelial-Mesenchymal Transition (EMT) process and inhibited stemness by up-regulating SFRP1.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Oncology
Yang Zhou, Jiang Xu, Haichang Luo, Xiangjing Meng, Ming Chen, Di Zhu
Summary: Abnormal activation of the Wnt/beta-catenin signaling pathway is closely related to tumorigenesis and immune surveillance, leading to increased resistance to immunotherapy.
Review
Chemistry, Medicinal
Zhen Wang, Zilu Li, Haitao Ji
Summary: Aberrant activation of the Wnt/beta-catenin signaling pathway is associated with cancer, and direct targeting of beta-catenin is a promising strategy but challenging. Research has identified potential small-molecule binding sites and summarized bioactive small molecules that target beta-catenin directly.
MEDICINAL RESEARCH REVIEWS
(2021)
Review
Biochemistry & Molecular Biology
Yoshifumi Takahata, Hiromasa Hagino, Ayaka Kimura, Mitsuki Urushizaki, Shiori Yamamoto, Kanta Wakamori, Tomohiko Murakami, Kenji Hata, Riko Nishimura
Summary: This review article summarizes the research progress on the functions and regulatory mechanisms of lubricin and growth differentiation factor 5 (Gdf5) in osteoarthritis (OA), as well as their roles in maintaining articular cartilage homeostasis and the development of OA. Molecular targeting of Prg4 and Gdf5 is expected to provide new insights into the etiology, pathogenesis, and potential treatment of OA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Qiyun Xiao, Johannes Werner, Nachiyappan Venkatachalam, Kim E. Boonekamp, Matthias P. Ebert, Tianzuo Zhan
Summary: Targeting cancer hallmarks is crucial for improving anti-cancer treatment, but cross-talk between signaling pathways often leads to resistance. This article provides an overview of the molecular interactions between the p53 and Wnt pathways in cancer, including complex feedback loops and reciprocal transactivation, as well as the mutational landscape of genes associated with these pathways.
Article
Oncology
Fei Yue, Weiyu Jiang, Amy T. Ku, Adelaide I. J. Young, Weijie Zhang, Eric P. Souto, Yankun Gao, Zihan Yu, Yi Wang, Chad J. Creighton, Chandandeep Nagi, Tao Wang, Susan G. Hilsenbeck, Xin-Hua Feng, Shixia Huang, Cristian Coarfa, Xiang H-F Zhang, Qingyun Liu, Xia Lin, Yi Li
Summary: The mechanism by which LGR4 promotes cancer metastasis is independent of the Wnt signaling pathway and involves interaction with EGFR to block its degradation, leading to increased migration and invasion of cancer cells.
Article
Oncology
Qi Sun, Boxin Liu, Quanxue Lan, Zijie Su, Qiuxia Fu, Lian Wang, Yingying Deng, Chuanli Li, Vivian Weiwen Xue, Shanshan Liu, Xianxiong Chen, Guowu Yang, Desheng Lu
Summary: The study revealed that chloroxylenol could inhibit the Wnt/beta-catenin signaling pathway, leading to anti-tumor effects in colorectal cancer cells, including inhibition of proliferation and migration, induction of apoptosis, and suppression of stemness.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ellen Youngsoo Rim, Hans Clevers, Roel Nusse
Summary: The Wnt pathway plays a central role in developmental and disease-related processes, regulating the generation and spatial arrangement of different cell types. Through regulation of cell fate, mitotic activity, and cell polarity, Wnt signaling coordinates development and tissue homeostasis, and its dysregulation is implicated in various disorders. This review summarizes the advances in our understanding of this pathway, from Wnt protein production to signal transduction in receiving cells. The evolutionary history of this pathway, as well as its regulators, and the remaining gaps in knowledge are discussed, highlighting directions for future research.
ANNUAL REVIEW OF BIOCHEMISTRY
(2022)
Review
Oncology
Iram Fatima, Susmita Barman, Rajani Rai, Kristina W. Thiel, Vishal Chandra
Summary: The role of Wnt signaling in endometrial carcinoma, including its activation mechanisms and links to cell cycle regulation, hormonal pathways, and other signaling cascades, remains a significant research focus. Therapeutic interference with Wnt signaling poses a challenge, and further advancements in drug discovery are needed.
Article
Biochemistry & Molecular Biology
Hongjuan You, Qi Li, Delong Kong, Xiangye Liu, Fanyun Kong, Kuiyang Zheng, Renxian Tang
Summary: Canonical Wnt/beta-catenin signaling is crucial in various cancers. Lysine acetylation, including histone and non-histone acetylation, plays a significant role in modulating this signaling. Inhibitors targeting KATs and KDACs have shown anti-tumor effects by blocking Wnt/beta-catenin signaling. Lysine acetylation may be a potential target for cancer therapy.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2022)
Article
Biotechnology & Applied Microbiology
Xiao Yu, Zhaoshuo Li, Ruihua Bai, Fuxiang Tang
Summary: TCF3 promotes the progression of cervical cancer by activating the SIRT1-mediated beta-catenin signaling pathway, and the high expression of TCF3 in cervical cancer is associated with poor prognosis.
Article
Oncology
Chun Tang, Xuehui Wang, Changle Ji, Wenfang Zheng, Yunhe Yu, Xiaochong Deng, Xiqian Zhou, Lin Fang
Summary: The study demonstrated that miR-640 suppresses the tumorigenesis of breast cancer cells by regulating the Wnt/β-catenin signaling pathway, making it a potential novel target for targeted therapy in breast cancer.
FRONTIERS IN ONCOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Jian Zhang, Mengmeng Qin, Dan Yang, Lan Yuan, Xiajuan Zou, Wenbing Dai, Hua Zhang, Xueqing Wang, Bing He, Qiang Zhang
Summary: A large number of proteins are involved in the delivery and transport of nanomedicines, playing a key role in mediating drug delivery and ensuring drug safety. The EV/ER/Golgi/SV pathway was found to dominate the transcytosis of nanoparticles across the epithelial barrier. Furthermore, the association of the Wnt/beta-catenin signaling pathway with nanoparticle transportation was discovered, with the regulatory effect varying based on particle size.
Review
Medicine, Research & Experimental
Yong Ji, Jian Lv, Di Sun, Yufeng Huang
Summary: This review explores the significant role of the Wnt/β-catenin signaling pathway in colorectal cancer tumorigenesis, metastasis, and recurrence, as well as its potential value in diagnosis and therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Sandra Ortega Ugalde, Kerstin Wallraven, Alexander Speer, Wilbert Bitter, Tom N. Grossmann, Jan N. M. Commandeur
BIOCHEMICAL PHARMACOLOGY
(2020)
Article
Chemistry, Multidisciplinary
Mathias Wendt, Rosa Bellavita, Alan Gerber, Nina-Louisa Efrem, Thirza van Ramshorst, Nicholas M. Pearce, Paul R. J. Davey, Isabel Everard, Mercedes Vazquez-Chantada, Elisabetta Chiarparin, Paolo Grieco, Sven Hennig, Tom N. Grossmann
Summary: This study designed beta-sheet mimetics targeting intracellular protein beta-catenin, effectively inhibiting the Wnt signaling pathway. The presented design strategy can support the development of inhibitors for other beta-sheet-mediated protein-protein interactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Niall M. McLoughlin, Arne Kuepper, Saskia Neubacher, Tom N. Grossmann
Summary: Peptide-DNA conjugates designed for binding with RNA through Watson-Crick base pairing combined with peptide-mediated major groove recognition represent a structure-based approach to novel biomolecular assemblies. By designing two distinct conjugate families with tunable binding characteristics for adjacent binding to a specific RNA sequence, a ternary complex is formed. The proximity of peptide elements in the complex enables an RNA-templated click reaction, introducing a new approach for functional biomolecular assemblies.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Anissa Haim, Saskia Neubacher, Tom N. Grossmann
Summary: Proteins require enforced tertiary structures to ensure stability for biotechnological and biomedical purposes. Intramolecular crosslinks have proven efficient in stabilizing native protein folds.
Article
Chemistry, Medicinal
Rosa Bellavita, Bruno Casciaro, Salvatore Di Maro, Diego Brancaccio, Alfonso Carotenuto, Annarita Falanga, Floriana Cappiello, Elisabetta Buommino, Stefania Galdiero, Ettore Novellino, Tom N. Grossmann, Maria Luisa Mangoni, Francesco Merlino, Paolo Grieco
Summary: This study aimed to increase the alpha-helicity content of temporin L by introducing diverse side-chain tethering strategies, leading to the development of novel cyclic analogues. The results showed that these cyclic analogues exhibited potential antimicrobial and cytotoxic activities, paving the way for the development of improved antibiotic cyclic AMP analogues.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Arne Kuepper, Niall M. McLoughlin, Saskia Neubacher, Alejandro Yeste-Vazquez, Estel Collado Camps, Chandran Nithin, Sunandan Mukherjee, Lucas Bethge, Janusz M. Bujnicki, Roland Brock, Stefan Heinrichs, Tom N. Grossmann
Summary: The design of high-affinity, RNA-binding ligands is challenging due to structural properties of RNA and lack of well-defined binding pockets. Peptide-derived molecules show promise as alternative scaffolds, but are limited by lack of design principles and bio-stability. Constrained alpha-helical peptides, like the one derived from TAV2b, show potential in mimicking RNA-binding proteins for the design of bioactive RNA-targeting ligands.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Infectious Diseases
Gina K. Schouten, Felix M. Paulussen, Oscar P. Kuipers, Wilbert Bitter, Tom N. Grossmann, Peter van Ulsen
Summary: The rising incidence of multidrug resistance in Gram-negative bacteria calls for novel treatment options. One promising approach is the combination of antibiotics with antimicrobial peptides. However, the use of such peptides is challenging due to their susceptibility to proteolytic degradation. This study demonstrates that the introduction of a hydrocarbon staple can enhance the stability and therapeutic potential of antimicrobial peptides without increasing their toxicity or hemolytic activity.
Article
Chemistry, Multidisciplinary
Felix M. Paulussen, Gina K. Schouten, Carolin Moertl, Jolanda Verheul, Irma Hoekstra, Gregory M. Koningstein, George H. Hutchins, Aslihan Alkir, Rosa A. Luirink, Daan P. Geerke, Peter van Ulsen, Tanneke den Blaauwen, Joen Luirink, Tom N. Grossmann
Summary: This study reports the structure-based design of a covalent inhibitor with high affinity for the bacterial divisome. The inhibitor showed inhibitory effects on the growth of E. coli strain and the infection of zebrafish larvae. This research provides new insights for the development of antibiotics targeting protein-protein interactions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Emma M. R. Koelman, Alejandro Yeste-Vazquez, Tom N. Grossmann
Summary: The Wnt/β-catenin signaling pathway plays a crucial role in embryonic development, stem cell maintenance, and tissue renewal. Hyperactivation of this pathway is linked to the development of various types of cancers. Inhibiting the protein-protein interaction involving β-catenin is a promising strategy for deactivating oncogenic Wnt signaling.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Felix M. Paulussen, Tom N. Grossmann
Summary: Protein-protein interactions play a role in cellular processes and are potential therapeutic targets. However, identifying small molecular inhibitors for these interactions is challenging due to the often large and flat interaction areas. Peptide interaction motifs can serve as starting points for inhibitor development, and irreversible peptide-based ligands have gained attention in recent years.
JOURNAL OF PEPTIDE SCIENCE
(2022)
Article
Biochemical Research Methods
Sebastian Kiehstaller, George H. Hutchins, Alessia Amore, Alan Gerber, Mohamed Ibrahim, Sven Hennig, Saskia Neubacher, Tom N. Grossmann
Summary: Enzymes are crucial for biotechnological and biomedical applications, but conditions necessary for many applications inhibit enzyme folding and function. This study stabilized a previously reported activity-enhanced Sortase A enzyme using the INCYPRO approach. The resulting bicyclic INCYPRO Sortase A enzyme demonstrated activity at elevated temperature and in the presence of chemical denaturants, unlike the wild-type and activity-enhanced versions.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Niall M. Mcloughlin, Marvin A. Albers, Estel Collado Camps, Jannik Paulus, Youri A. Ran, Saskia Neubacher, Sven Hennig, Roland Brock, Tom N. Grossmann
Summary: Double-stranded RNAs (dsRNA), potential therapeutic molecules, suffer from low stability and poor cellular uptake. Researchers have designed dimeric stapled peptides based on the RNA-binding protein TAV2b, which can bind and stabilize dsRNA, protect it from degradation, and promote cellular uptake. These findings demonstrate the potential of peptide-based RNA binders for the stabilization and protection of dsRNA, expanding the applicability of dsRNA for therapeutic purposes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Nicolas Brauckhoff, Laura Fang, Anissa Haim, Tom N. Grossmann
Summary: This article presents a method using non-enzymatic protein as a template for amide bond formation, demonstrating its potential as a novel tool for selectively modifying proteins through selective labeling of a target protein.
CHEMICAL COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Helene Adihou, Ranganath Gopalakrishnan, Tim Foerster, Stephanie M. Gueret, Raphael Gasper, Stefan Geschwindner, Carmen Carrillo Garcia, Hacer Karatas, Ajaybabu Pobbati, Mercedes Vazquez-Chantada, Paul Davey, Carola M. Wassvik, Jeremy Kah Sheng Pang, Boon Seng Soh, Wanjin Hong, Elisabetta Chiarparin, Dennis Schade, Alleyn T. Plowright, Eric Valeur, Malin Lemurell, Tom N. Grossmann, Herbert Waldmann
NATURE COMMUNICATIONS
(2020)
Article
Chemistry, Multidisciplinary
Kerstin Wallraven, Fredrik L. Holmelin, Adrian Glas, Sven Hennig, Andrey I. Frolov, Tom N. Grossmann