Article
Biochemistry & Molecular Biology
Zekai Kong, Min Xu, Yanqing Zhang, Wenda Huang, Xiaolu Zhao, Jie Luo, Bao-Liang Song
Summary: The Hedgehog signaling pathway relies on the activation of Smoothened (SMO) through cholesterol modification. This study identifies key residues, including D95, Y130, Y85, T88, T90, W109, W119, K133, E160, and F166, involved in the cholesterol modification of SMO. In particular, a cation-pi interaction between Y85 and K133 is found to be crucial for SMO cholesterylation and ciliary localization.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Review
Oncology
Sheikh A. A. Umar, Bo Dong, Minakshi Nihal, Hao Chang
Summary: This review summarizes the role of FZD receptors in melanoma, including their involvement in embryonic development, tissue homeostasis, and cancer. Misregulated FZD signaling promotes tumor cell proliferation and invasion in melanoma, and both the canonical and non-canonical pathways are implicated.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Stephane Angers
Summary: This study reveals a Wnt-stimulated positive feedback loop involving local production and recruitment of PI(4,5)P-2 to facilitate LRP5/6 phosphorylation.
Article
Cell Biology
Pablo Astudillo
Summary: This study analyzed the role of the Wnt signaling pathways in gastric cancer and identified a WNT5A/FZD2/FZD7/ROR2 signature associated with tumor-infiltrating and mesenchymal cell marker expression. High expression of FZD7 and ROR2 correlated with a shared gene and protein expression profile, which in turn correlated with poor prognosis. Overall, the findings provide an updated perspective on the contributions of the Wnt/beta-catenin and non-canonical Wnt pathways in gastric cancer.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Francesca Manuela Johnson de Sousa Brito, Andrew Butcher, Addolorata Pisconti, Blandine Poulet, Amanda Prior, Gemma Charlesworth, Catherine Sperinck, Michele Scotto di Mase, Ke Liu, George Bou-Gharios, Robert Jurgen van 't Hof, Anna Daroszewska
Summary: Syndecan-3 promotes new bone formation in osteoblasts by enhancing WNT signaling, and its deficiency in mice results in an early osteoporosis-like phenotype due to delayed osteoblast maturation and impaired function. Overexpressing Sdc3 in osteoblasts rescues the low bone volume phenotype and increases bone mass, making SDC3 a potential target for novel bone anabolic drug development.
Review
Cell Biology
Shefali Mehta, Swapnil Hingole, Varun Chaudhary
Summary: Wnt proteins are lipid-modified secreted proteins that activate multiple signaling pathways, regulating crucial processes during development. Despite being hydrophobic, they can travel several cell distances in the extracellular space. Research has identified factors and mechanisms regulating their expression, secretion, and extracellular travel, recognizing the importance of Wnt protein gradients in maintaining tissue homeostasis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Yagmur Azbazdar, Mustafa Karabicici, Esra Erdal, Gunes Ozhan
Summary: Wnt signaling pathway plays a crucial role in physiological activities and has significant implications in cancer development and progression. By regulating plasma membrane composition and lipid organization, Wnt signaling can be activated or inhibited, leading to the development of more targeted anticancer drugs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Alexander Girich, Konstantin Sadriev, Lidia Frolova, Igor Dolmatov
Summary: The study investigated the sfrp and smo genes and their role in the regeneration process of internal organs in the holothurian Eupentacta fraudatrix. Two sfrp genes (sfrp1/2/5, sfrp3/4) and one smo gene were identified in this species. Knockdown of these genes using RNA interference disrupted the formation of aquapharyngeal bulb (AB) in regeneration. Knockdown of sfrp1/2/5 affected the extracellular matrix remodelling and cell migration in AB, while knockdown of sfrp3/4 disrupted the connective tissue and symmetry of AB anlage. Knockdown of smo impaired AB regeneration and prevented the formation of connections between ambulacras. However, regeneration of the digestive tube and AB was independent of each other.
WOUND REPAIR AND REGENERATION
(2023)
Article
Immunology
Safaa A. Faheem, Reem M. Hazem, Norhan M. Elsayed, Yasser M. Ahmed, Noha M. Saeed
Summary: The study aimed to assess the involvement of Wnt/beta-catenin signaling in CsA-induced hepatotoxicity and whether knockdown of this pathway by NCL can attenuate CsA-induced hepatotoxicity. The results showed that NCL can significantly decrease liver enzymes activities, improve histopathological alterations induced by CsA, alleviate oxidative stress and inflammation. Moreover, NCL inhibited Wnt/beta-catenin signaling and increased the expression of PPAR-gamma.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Medicine, Research & Experimental
Wenqiang Zhang, Kexin Zhang, Yanhui Ma, Yixin Song, Tongbing Qi, Guoji Xiong, Yuanzhu Zhang, Chengxia Kan, Jingwen Zhang, Fang Han, Xiaodong Sun
Summary: This review examines the expression patterns of SFRPs in cancer and their potential as therapeutic targets, summarizing the current knowledge on SFRPs in cancer.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Genetics & Heredity
Li-Ping Li, Bo Zhang, Li Cheng
Summary: Identification and characterization of plant protein-protein interactions (PPIs) are crucial in understanding protein functions and molecular mechanisms in plant cells. This article proposes a computational framework, CPIELA, for predicting plant PPIs, which combines PSSM, LOOP, and ROF model. Experimental results demonstrate that CPIELA achieved high prediction accuracies and outperforms other state-of-the-art methods. CPIELA has the potential to be a useful tool in identifying possible plant PPIs.
FRONTIERS IN GENETICS
(2022)
Article
Chemistry, Multidisciplinary
Shaoqin Zheng, Jiahui Lin, Zhongqiu Pang, Hui Zhang, Yinuo Wang, Lanjing Ma, Haijiao Zhang, Xi Zhang, Maorong Chen, Xinjun Zhang, Chao Zhao, Jun Qi, Liu Cao, Min Wang, Xi He, Ren Sheng
Summary: In this study, researchers discovered that cholesterol binds specifically to the Fzd5 receptor, enabling its maturation and trafficking to the plasma membrane. Cholesterol stimulates tumor growth in Wnt-addicted pancreatic ductal adenocarcinoma through Fzd5-mediated signaling, while a natural compound can inhibit this process. These findings reveal a novel mechanism by which Fzd5 acts as a cholesterol sensor and suggest potential therapeutic opportunities for Wnt-dependent cancers.
Article
Medicine, General & Internal
Chao Yin, Zhishuai Ye, Jian Wu, Chenxing Huang, Le Pan, Huaiyu Ding, Lei Zhong, Lei Guo, Yan Zou, Xiang Wang, Ying Wang, Pan Gao, Xuejuan Jin, Xiaoxiang Yan, Yunzeng Zou, Rongchong Huang, Hui Gong
Summary: The study found that elevated levels of Wnt2 and Wnt4 in the serum of AMI patients were associated with adverse outcomes. Wnt2 and Wnt4 promote cardiac fibrosis by activating the beta-catenin/NF-kappa B signaling pathway, potentially impacting the cardiac function of AMI patients.
Article
Endocrinology & Metabolism
Sung-Jin Bae, Yunju Jo, Min Kyoung Cho, Jung-Sook Jin, Jin-Young Kim, Jaewon Shim, Yun Hak Kim, Jang-Kyung Park, Dongryeol Ryu, Hyun Joo Lee, Jongkil Joo, Ki-Tae Ha
Summary: Endometriosis is a common gynecological disease, and its underlying mechanisms are not fully understood. This study identified differentially expressed genes associated with endometriosis and revealed multiple signaling pathways involved in its pathogenesis. Validation of gene expression was also done through immunohistochemistry and western blot analysis.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chaohui Zhang, Yuxin Li, Jiaheng Cao, Beibei Yu, Kaiyue Zhang, Ke Li, Xinhui Xu, Zhikun Guo, Yinming Liang, Xiao Yang, Zhongzhou Yang, Yunfu Sun, Vesa Kaartinen, Keyue Ding, Jikui Wang
Summary: The study reveals that Smoothened-mediated hedgehog signaling controls posterior cardiac progenitor commitment, suggesting that Smoothened mutation may be involved in the etiology of congenital heart diseases related to the cardiac conduction system and heart valves.
Article
Biochemistry & Molecular Biology
Sebastian Other-Gee Pohl, Shazib Pervaiz, Arun Dharmarajan, Mark Agostino
Article
Genetics & Heredity
Isabel A. Hemming, Olivier Clement, Ivan E. Gladwyn-Ng, Hayley D. Cullen, Han Leng Ng, Heng B. See, Linh Ngo, Daniela Ulgiati, Kevin D. G. Pfleger, Mark Agostino, Julian I-T. Heng
Review
Biochemistry & Molecular Biology
Mark Agostino, Sebastian Other-Gee Pohl
BIOCHEMICAL SOCIETY TRANSACTIONS
(2020)
Article
Genetics & Heredity
Isabel A. Hemming, Steven Blake, Mark Agostino, Julian I-T Heng
Article
Biochemistry & Molecular Biology
Mark Agostino
CARBOHYDRATE RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Steven Blake, Isabel Hemming, Julian Ik-Tsen Heng, Mark Agostino
Summary: The Cys(2)His(2) type zinc finger is a common motif in transcription factor proteins, facilitating DNA binding to influence gene expression. ZBTB18 is a transcription factor involved in mammalian tissue development, and disease-associated missense variants in its zinc finger domain can disrupt transcriptional regulation and neural circuit formation. Structure-based approaches like thermodynamic integration and Residue Scanning are effective in distinguishing between disease-associated and general population ZBTB18 missense variants.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Victoria Gudino, Sebastian Other-Gee Pohl, Caroline V. Billard, Patrizia Cammareri, Alfonso Bolado, Stuart Aitken, David Stevenson, Adam E. Hall, Mark Agostino, John Cassidy, Colin Nixon, Alex von Kriegsheim, Paz Freile, Linda Popplewell, George Dickson, Laura Murphy, Ann Wheeler, Malcolm Dunlop, Farhat Din, Douglas Strathdee, Owen J. Sansom, Kevin B. Myant
Summary: Current therapeutic options for colorectal cancer are limited in efficacy, often resulting in acquired resistance during treatment. Research has identified RAC1B as a key mediator of colorectal tumourigenesis and a potential target for enhancing EGFR inhibitor treatment. Inhibition of RAC1B has been shown to sensitize cetuximab-resistant colorectal cancer cells to EGFR inhibitors, presenting a promising therapeutic target for improving clinical efficacy.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Adam E. Hall, Sebastian Other-Gee Pohl, Patrizia Cammareri, Stuart Aitken, Nicholas T. Younger, Michela Raponi, Caroline V. Billard, Alfonso Bolado Carrancio, Aslihan Bastem, Paz Freile, Fiona Haward, Ian R. Adams, Javier F. Caceres, Paula Preyzner, Alex von Kriegsheim, Malcolm G. Dunlop, Farhat V. Din, Kevin B. Myant
Summary: This study identifies dysregulated RNA splicing as a key driver of tumour cell plasticity in colorectal cancer. The splicing factor SRSF1 controls Kras splicing and maintains stemness in CRC cells, and its expression correlates with cancer stem cell markers in human tumours.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Mark Agostino, Sebastian Other-Gee Pohl
ORGANIC & BIOMOLECULAR CHEMISTRY
(2020)
