Article
Biochemistry & Molecular Biology
Michael D. Paul, Kalina Hristova
Summary: This study proposes a provocative hypothesis that active, ligand-bound RTK dimers from unrelated subfamilies can associate into heterooligomers with novel signaling properties, supported by quantitative FRET study. Direct interactions between EGFR and VEGFR2 are observed in the absence of ligand and in the presence of both ligands, suggesting a novel mechanism for signal diversification.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Cell Biology
Christopher Xie, Dipon K. Mondal, Mikdat Ulas, Thomas Neill, Renato Iozzo
Summary: Decorin is a prototype member of the small leucine-rich proteoglycan gene family derived from stromal cells. It functions as a regulator of collagen fibrillogenesis and TGF-beta activity, and also acts as a pan-receptor tyrosine kinase (RTK) inhibitor. Decorin binds to various RTKs and transiently activates them, suppressing downstream signaling cascades and leading to growth inhibition. Decorin also restricts cancer growth and dissemination by impeding angiogenesis and inducing endothelial cell autophagy. Overall, decorin has the potential to be used as a protein-based adjuvant therapy to combat cancer.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Thomas Neill, Aastha Kapoor, Christopher Xie, Simone Buraschi, Renato Iozzo
Summary: Proteoglycans and selected extracellular matrix constituents are emerging as critical regulators of autophagy, influencing various cell types by activating a dynamic signaling network. These matrix constituents, both proautophagic and anti-angiogenic, engage specific cell surface receptors and contribute to proper tissue homeostasis independently of nutrient availability. Their role in matrix-regulated autophagy can potentially be leveraged for therapeutic purposes in combating diseases.
Article
Dermatology
Xue Xu, Pin Ha, Emily Yen, Chenshuang Li, Zhong Zheng
Summary: Small leucine-rich proteoglycans (SLRPs) play a crucial role in regulating tendon structure and biomechanics, offering a promising method for tendon injury management. However, current knowledge on the role of SLRPs in tendon development and regeneration is limited, requiring further investigations.
ADVANCES IN WOUND CARE
(2022)
Review
Biochemistry & Molecular Biology
Shermaine W. Y. Low, Thomas B. Connor, Iris S. Kassem, Deborah M. Costakos, Shyam S. Chaurasia
Summary: Small leucine-rich proteoglycans (SLRPs) serve a crucial role in maintaining retinal homeostasis by participating in the organization of extracellular matrix, regulation of cell growth, and cell-matrix interactions in several upstream signaling pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Sandeep Appunni, Muni Rubens, Venkataraghavan Ramamoorthy, Vivek Anand, Madhuram Khandelwal, Alpana Sharma
Summary: Biglycan, as a class I SLRP, is a key component of the ECM involved in scaffolding collagen fibrils and mediating cell signaling. Dysregulation of its expression can lead to various clinical conditions including metabolic disorders, inflammatory disorders, musculoskeletal defects, and malignancies. Biglycan interacts with TLR-2 and TLR-4 on immune cells to induce inflammation, and its dysregulation is also observed in inflammatory metabolic conditions and cancer, where high expression levels facilitate tumor growth and metastasis.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Bihui Cao, Manting Liu, Lu Wang, Kangshun Zhu, Mingyue Cai, Xiaopei Chen, Yunfei Feng, Shuo Yang, Shengyu Fu, Cheng Zhi, Xiaodie Ye, Jian Zhang, Zhiru Zhang, Xin Yang, Ming Zhao, Qingde Wu, Linfeng Xu, Lili Yang, Hui Lian, Qi Zhao, Zhenfeng Zhang
Summary: The complex immunosuppressive tumor microenvironment and lack of tumor-specific targets hinder the application of CAR T cell therapy in solid tumors. AXL, highly expressed in NSCLC but not in normal tissues, might be a target for CAR T cell therapy. Combining microwave ablation and AXL-CAR T cells shows superior antitumor efficacy.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Omkulthom M. Alkamaly, Najla Altwaijry, Rehab Sabour, Marwa F. Harras
Summary: Novel derivatives of the pyrazoline scaffold showed significant and broad-spectrum anticancer activities with lower cytotoxicity against normal cells. Compounds 5b and 7c were identified as potent dual EGFR and VEGFR2 inhibitors, with strong apoptotic effects on cancer cells. The compounds also demonstrated potential as apoptosis inducers through molecular docking analyses.
ARCHIV DER PHARMAZIE
(2021)
Review
Chemistry, Analytical
Juan Gao, Jingyi Jian, Zhengjin Jiang, Ann Van Schepdael
Summary: Tyrosine kinases have been extensively studied as drug targets due to their regulation of cellular processes. The deregulation of tyrosine kinases plays a key role in the pathophysiology of various diseases. Several techniques, including traditional binding assays and high-throughput screening methods, have been developed to discover new tyrosine kinase inhibitors. This review provides insights into the different assay methods for the exploration of novel tyrosine kinase inhibitors.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Biology
Minseong Kim, Carmen Reinhard, Christof Niehrs
Summary: MET is identified as the kinase responsible for phosphorylating the 4Y motif in ZNRF3, leading to reduced degradation of Wnt receptors and enhanced Wnt/beta-catenin signaling. HGF-MET signaling phosphorylates ZNRF3, while PTPRK dephosphorylates it, regulating ZNRF3 internalization and functioning as a potential therapeutic target for Wnt signaling modulation.
Review
Oncology
Aikaterini Berdiaki, Eirini-Maria Giatagana, George Tzanakakis, Dragana Nikitovic
Summary: Cancer is a complex disease involving changes in cells and the surrounding environment. The tumor microenvironment consists of tumor cells, normal tissue cells, blood vessels, immune system cells, stromal cells, and the extracellular matrix (ECM). Small leucine-rich proteoglycans (SLRPs) are molecules released by cells into the surrounding matrix. They can interact with cell surface molecules and secreted biomolecules, altering signaling pathways and regulating cell behavior. This review focuses on the roles of two SLRP members, biglycan and lumican, and their impact on cancer cell survival, growth, and metastasis.
Article
Clinical Neurology
Shanmuganathan Rajasekaran, Dilip Chand Raja Soundararajan, Chitraa Tangavel, Sharon Miracle Nayagam, Sri K. S. Vijayanand, R. Sunmathi, Monica Steffi Matchado, Raveendran Muthurajan, Ajoy Prasad Shetty, Rishi Mugesh Kanna, K. Dharmalingam
Summary: This study utilized proteomic analysis to compare the expression of SLRPs in fetal, healthy adult, and degenerated discs. The results showed a universal decrease in SLRPs abundance in degenerated discs, associated with an increase in MMPs and a reduction in TIMPs. Fetal discs were mainly engaged in ribosomal pathways, while healthy adult discs primarily participated in ECM maintenance and basic metabolic pathways.
Article
Oncology
Miso Park, Ji Won Kim, Kyu Min Kim, Seungmin Kang, Wankyu Kim, Jin-Ki Kim, Youngnam Cho, Hyungjae Lee, Moon Chang Baek, Ju-Hyun Bae, Seung Hyun Lee, Sung Baek Jeong, Sung Chul Lim, Dae Won Jun, Sung Yun Cho, Yeonji Kim, Yong June Choi, Keon Wook Kang
Summary: This study reveals that csEVs facilitate cancer cell migration and chemoresistance through TYRO3 activation, suggesting a potential therapeutic target for aggressive cancers.
Article
Immunology
Yu-Xiang Ma, Fu-Rong Liu, Yang Zhang, Qun Chen, Zhi-Qiang Chen, Qian-Wen Liu, Yan Huang, Yun-Peng Yang, Wen-Feng Fang, Ning Xi, Ning Kang, Yu-Lei Zhuang, Qi Zhang, Ying-Zhi Jiang, Li Zhang, Hong-Yun Zhao
Summary: CT053PTSA is a novel tyrosine kinase inhibitor that shows promising antitumor and antiangiogenic activity. The first-in-human study demonstrated that CT053PTSA is well tolerated and has a satisfactory safety profile. Further clinical trials are ongoing to evaluate the clinical activity of CT053PTSA.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Xinran Li, Amy Y. T. Lau, Angel S. N. Ng, Abdullah Aldehaiman, Yuan Zhou, Patrick K. S. Ng, Stefan T. Arold, Lydia W. T. Cheung
Summary: The study demonstrates that driver mutations in p85α can activate multiple kinase pathways and promote malignant growth of cancer cells. These mutations increase HER3 protein levels by inhibiting HER3 ubiquitination and degradation, leading to its heterodimerization with EGFR, HER2, and c-Met, as well as the allosteric activation of these dimerized partners.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Thomas Neill, Simone Buraschi, Atul Goyal, Catherine Sharpe, Elizabeth Natkanski, Liliana Schaefer, Andrea Morrione, Renato V. Iozzo
JOURNAL OF CELL BIOLOGY
(2016)
Article
Oncology
Simone Buraschi, Shi-Qiong Xu, Manuela Stefanello, Igor Moskalev, Alaide Morcavallo, Marco Genua, Ryuta Tanimoto, Ruth Birbe, Stephen C. Peiper, Leonard. G. Gomella, Antonino Belfiore, Peter C. Black, Renato V. Iozzo, Andrea Morrione
Article
Endocrinology & Metabolism
Ryuta Tanimoto, Kuojung G. Lu, Shi-Qiong Xu, Simone Buraschi, Antonino Belfiore, Renato V. Iozzo, Andrea Morrione
FRONTIERS IN ENDOCRINOLOGY
(2016)
Article
Biochemistry & Molecular Biology
Ryuta Tanimoto, Chiara Palladino, Shi-Qiong Xu, Simone Buraschi, Thomas Neill, Leonard G. Gomella, Stephen C. Peiper, Antonino Belfiore, Renato V. Lozzo, Andrea Morrione
Article
Biochemistry & Molecular Biology
Theodoros T. Karalis, Paraskevi Heldin, Demitrios H. Vynios, Thomas Neill, Simone Buraschi, Renato V. Iozzo, Nikos K. Karamanos, Spyros S. Skandalis
Review
Biochemistry & Molecular Biology
Alberto Passi, Davide Vigetti, Simone Buraschi, Renato V. Iozzo
Review
Oncology
Maria A. Gubbiotti, Simone Buraschi, Aastha Kapoor, Renato Iozzo
SEMINARS IN CANCER BIOLOGY
(2020)
Article
Immunology
Chiara Tobia, Paola Chiodelli, Andrea Barbieri, Simone Buraschi, Elena Ferrari, Stefania Mitola, Giuseppe Borsani, Jessica Guerra, Marco Presta
FRONTIERS IN IMMUNOLOGY
(2019)
Review
Biochemistry & Molecular Biology
Maurizio Mongiat, Simone Buraschi, Eva Andreuzzi, Thomas Neill, Renato Iozzo
BIOCHEMICAL SOCIETY TRANSACTIONS
(2019)
Article
Biochemistry & Molecular Biology
Thomas Neill, Carolyn G. Chen, Simone Buraschi, Renato V. Iozzo
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Simone Buraschi, Thomas Neill, Shi-Qiong Xu, Chiara Palladino, Antonino Bel, Renato V. Iozzo, Andrea Morrione
Review
Cell Biology
Thomas Neill, Simone Buraschi, Aastha Kapoor, Renato V. Iozzo
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Liping Mao, Jinxue Yang, Jiaxin Yue, Yang Chen, Hongrui Zhou, Dongdong Fan, Qiuhua Zhang, Simone Buraschi, Renato V. Iozzo, Xiuli Bi
Summary: The study reveals the significant role of a decorin-deficient tumor microenvironment in colon carcinoma progression and metastasis, with promising therapeutic efficacy demonstrated in decorin-deficient animals through a combined Celecoxib/decorin treatment.
Article
Oncology
Tu Dan, Anuradha A. Shastri, Ajay Palagani, Simone Buraschi, Thomas Neill, Jason E. Savage, Aastha Kapoor, Tiziana DeAngelis, Sankar Addya, Kevin Camphausen, Renato Iozzo, Nicole L. Simone
Summary: Research has shown that miR-21 plays a crucial role in the development and treatment of breast cancer, with its knockout inhibiting tumor growth and metastasis, and increasing tumor sensitivity to radiotherapy and chemotherapy.