Article
Cell Biology
Zhe Qian, Dongyan Song, Jonathan J. Ipsaro, Carmelita Bautista, Leemor Joshua-Tor, Johannes T. -H. Yeh, Nicholas K. Tonks
Summary: In this study, the researchers generated a novel monoclonal antibody, RD-43, which targeted the ectodomain of PTPRD to inhibit its function and promote its degradation. Treatment with RD-43 was found to suppress SRC signaling required for breast cancer cell invasion. These findings suggest that antibodies targeting extracellular segments of receptor protein tyrosine phosphatases may have therapeutic potential.
GENES & DEVELOPMENT
(2023)
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
Biochemistry & Molecular Biology
Yan Xu, Dorothea Robev, Nayanendu Saha, Bingcheng Wang, Matthew B. Dalva, Kai Xu, Juha P. Himanen, Dimitar B. Nikolov
Summary: Eph receptor tyrosine kinases and ephrin ligands play crucial roles in cell communication, with dysfunctional signaling leading to disease. The formation of extensive signaling assemblies regulates neuronal migration and axon pathfinding.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Manae Tatsumi, Takayuki Kishi, Satoru Ishida, Hiroki Kawana, Akiharu Uwamizu, Yuki Ono, Kouki Kawakami, Junken Aoki, Asuka Inoue
Summary: A method previously used for detecting GPCR activation has been shown to also detect TRP channel activation. The method is simple, low-cost, and only requires an absorbance microplate reader. Using substrates of ADAM10, such as EGF and BTC, improves the specificity of the assay.
Article
Medicine, Research & Experimental
Huw J. Morgan, Elise Rees, Simone Lanfredini, Kate A. Powell, Jasmine Gore, Alex Gibbs, Charlotte Lovatt, Gemma E. Davies, Carlotta Olivero, Boris Y. Shorning, Giusy Tornillo, Alex Tonks, Richard Darley, Eddie C. Y. Wang, Girish K. Patel
Summary: This study found that CD200 protein in basal cell carcinoma may lead to the near absence of NK cells in the tumor microenvironment through ectodomain shedding. CD200 suppresses MAPK signaling in NK cells, blocking indirect and direct cell killing. Blocking CD200 inhibition can restore NK cell killing ability.
JOURNAL OF CLINICAL INVESTIGATION
(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
Oncology
Maria J. De Herdt, Berdine van der Steen, Robert J. Baatenburg de Jong, Leendert H. J. Looijenga, Senada Koljenovic, Jose A. Hardillo
Summary: Head and neck cancer, particularly oral cancer, is a common type of cancer with a low survival rate. Targeted therapies that focus on the MET protein have gained attention, but the lack of companion diagnostics complicates treatment. Shedding of the ectodomain of MET and its association with poor prognosis in oral squamous cell carcinoma highlight the importance of investigating MET-EC- and incorporating it into companion diagnostics.
Article
Biochemistry & Molecular Biology
Xiang Ma, Yusuke Takahashi, Wenjing Wu, Wentao Liang, Jianglei Chen, Dibyendu Chakraborty, Yangxiong Li, Yanhong Du, Siribhinya Benyajati, Jian-Xing Ma
Summary: This study demonstrates that ADAM17 is responsible for shedding the soluble ectodomain of VLDLR in human retinal pigment epithelium cells, which plays anti-inflammatory and anti-angiogenic roles through inhibition of Wnt signaling. Inhibition of ADAM17 reduces sVLDLR levels in ocular tissues, suggesting it as a potential therapeutic target for disorders associated with dysregulation of Wnt signaling.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Neurosciences
Dolores Martin-de-Saavedra, Marc Dos Santos, Peter Penzes
Summary: This article provides an overview of the importance of ectodomain shedding in the nervous system, discussing the role of synaptic ectodomain shedding in autocrine and paracrine signaling. The article also highlights the use of cerebrospinal fluid analysis for identifying potential biomarkers for neuropsychiatric disorders.
TRENDS IN NEUROSCIENCES
(2022)
Article
Multidisciplinary Sciences
Kazuya Tsumagari, Chih-Hsiang Chang, Yasushi Ishihama
Summary: Ectodomain shedding is a proteolytic process that regulates membrane protein levels and functions. Dysregulated shedding is associated with severe diseases such as cancer and Alzheimer's disease. By generating large-scale, cell-type-specific maps of shedding cleavage sites, we identified a significant number of cell-type-specific cleavage sites.
Review
Oncology
Lucia Gandullo-Sanchez, Alberto Ocana, Atanasio Pandiella
Summary: HER3 protein is closely associated with the development of various tumors, and targeting HER3 has therapeutic relevance in promoting cell proliferation. Different types of agents targeting HER3 have been developed, including antibodies, aptamers, and vaccines. This article reviews the preclinical and clinical development of drugs targeting HER3.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
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
Multidisciplinary Sciences
Erik Klapproth, Anke Witt, Pauline Klose, Johanna Wiedemann, Nikitha Vavilthota, Stephan R. Kuenzel, Susanne Kaemmerer, Mario Guenscht, David Sprott, Mathias Lesche, Fabian Rost, Andreas Dahl, Erik Rauch, Lars Kattner, Silvio Weber, Peter Mirtschink, Irakli Kopaliani, Kaomei Guan, Kristina Lorenz, Paul Saftig, Michael Wagner, Ali El-Armouche
Summary: After myocardial infarction, targeting the ADAM10/CX3CL1 axis can help regulate neutrophil recruitment, improve heart function, and reduce scar size by reducing inflammation and neutrophil infiltration.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Li Chen, Xiangyi Kong, Yi Fang, Shishir Paunikar, Xiangyu Wang, James A. L. Brown, Emer Bourke, Xingrui Li, Jing Wang
Summary: Discoidin domain receptor tyrosine kinases (DDRs) are a type of receptor tyrosine kinases associated with various diseases, widely expressed in different cell types and involved in signaling pathways, closely related to the development and progression of solid tumors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Alida Besch, William M. Marsiglia, Moosa Mohammadi, Yingkai Zhang, Nathaniel J. Traaseth
Summary: Many human cancers are treated with small molecule inhibitors that target the kinase domain of receptor tyrosine kinases. Long-term treatment often leads to drug resistance mutations at the gatekeeper residue, increasing the aggressiveness of the cancer. However, the mechanism of gain-of-function by gatekeeper mutations is poorly understood.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Samatha Bhat, Shama Prasada Kabekkodu, Ashish Noronha, Kapaettu Satyamoorthy
Article
Oncology
Donatella Romaniello, Luigi Mazzeo, Maicol Mancini, Ilaria Marrocco, Ashish Noronha, Matthew Kreitman, Swati Srivastava, Soma Ghosh, Moshit Lindzen, Tomer Meir Salame, Amir Onn, Jair Bar, Yosef Yarden
CLINICAL CANCER RESEARCH
(2018)
Article
Biochemistry & Molecular Biology
Lee Roth, Swati Srivastava, Moshit Lindzen, Aldema Sas-Chen, Michal Sheffer, Mattia Lauriola, Yehoshua Enuka, Ashish Noronha, Maicol Mancini, Sara Lavi, Gabi Tarcic, Gur Pines, Nava Nevo, Ori Heyman, Tamar Ziv, Oscar M. Rueda, Davide Gnocchi, Eli Pikarski, Arie Admon, Carlos Caldas, Yosef Yarden
Article
Biochemistry & Molecular Biology
Lee Roth, Swati Srivastava, Moshit Lindzen, Aldema Sas-Chen, Michal Sheffer, Mattia Lauriola, Yehoshua Enuka, Ashish Noronha, Maicol Mancini, Sara Lavi, Gabi Tarcic, Gur Pines, Nava Nevo, Ori Heyman, Tamar Ziv, Oscar M. Rueda, Davide Gnocchi, Eli Pikarski, Arie Admon, Carlos Caldas, Yosef Yarden
Article
Biochemistry & Molecular Biology
Ruth Maron, Bilha Schechter, Nishanth Belugali Nataraj, Soma Ghosh, Donatella Romaniello, Ilaria Marrocco, Ashish Noronha, Silvia Carvalho, Yosef Yarden, Michael Sela
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2019)
Article
Oncology
Simone Borgoni, Emre Sofyali, Maryam Soleimani, Heike Wilhelm, Karin Mueller-Decker, Rainer Will, Ashish Noronha, Lukas Beumers, Pernette J. Verschure, Yosef Yarden, Luca Magnani, Antoine H. C. van Kampen, Perry D. Moerland, Stefan Wiemann
Article
Oncology
Yuya Haga, Ilaria Marrocco, Ashish Noronha, Mary Luz Uribe, Nishanth Belugali Nataraj, Arunachalam Sekar, Diana Drago-Garcia, Simone Borgoni, Moshit Lindzen, Suvendu Giri, Stefan Wiemann, Yasuo Tsutsumi, Yosef Yarden
Summary: This study reveals an unconventional mechanism of resistance to dacomitinib in lung cancer cells and uncovers a previously unknown step of resistance acquisition. The resistant cells did not acquire secondary mutations in EGFR but displayed characteristics of epithelial-mesenchymal transition. Interestingly, when implanted in animals, the resistant cells reverted to a dacomitinib-sensitive state, but regained resistance when cultured in vitro.
Article
Biochemistry & Molecular Biology
Moshit Lindzen, Soma Ghosh, Ashish Noronha, Diana Drago, Nishanth Belugali Nataraj, Orith Leitner, Silvia Carvalho, Einav Zmora, Stav Sapoznik, Keren Bahar Shany, Keren Levanon, Dan Aderka, Belinda Sanchez Ramirez, Maik Dahlhoff, Iain McNeish, Yosef Yarden
Summary: Research suggests that AREG is overexpressed in abdominal fluids of ovarian cancer patients, and its immune modulation is associated with animal survival. The generation of a new antibody to target AREG has extended the survival time of mice.
Article
Biochemistry & Molecular Biology
Anamika Singh, Ariel Erijman, Ashish Noronha, Hemant Kumar, Yoav Peleg, Yosef Yarden, Julia M. Shifman
Summary: The study demonstrates that engineered RASSF5 variants can inhibit Ras-regulated procancer pathways and stimulate anticancer processes, providing an attractive therapeutic strategy against cancer development.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Nishanth Belugali Nataraj, Ashish Noronha, Joo Sang Lee, Soma Ghosh, Harsha Raj Mohan Raju, Arunachalam Sekar, Binyamin Zuckerman, Moshit Lindzen, Emilio Tarcitano, Swati Srivastava, Michael Selitrennik, Ido Livneh, Diana Drago-Garcia, Oscar Rueda, Carlos Caldas, Sima Lev, Tamar Geiger, Aaron Ciechanover, Igor Ulitsky, Rony Seger, Eytan Ruppin, Yosef Yarden
Summary: By establishing multi-omics pipelines, we discovered that overexpression of NUP93 is associated with aggressive human mammary tumors, enhancing their migration and invasion capabilities. NUP93 is involved in nuclear transport, activating various signaling pathways and ultimately contributing to tumor growth and metastasis. Targeting this nuclear transport process with myristoylated peptides can inhibit tumor growth and metastasis.
Article
Oncology
Ashish Noronha, Nishanth Belugali Nataraj, Joo Sang Lee, Benny Zhitomirsky, Yaara Oren, Sara Oster, Moshit Lindzen, Saptaparna Mukherjee, Rainer Will, Soma Ghosh, Arturo Simoni-Nieves, Aakanksha Verma, Rishita Chatterjee, Simone Borgoni, Welles Robinson, Sanju Sinha, Alexander Brandis, D. Lucas Kerr, Wei Wu, Arunachalam Sekar, Suvendu Giri, Youngmin Chung, Diana Drago-Garcia, Brian P. Danysh, Mattia Lauriola, Michelangelo Fiorentino, Andrea Ardizzoni, Moshe Oren, Collin M. Blakely, Jideofor Ezike, Stefan Wiemann, Laxmi Parida, Trever G. Bivona, Rami Aqeilan, Joan S. Brugge, Aviv Regev, Gad Getz, Eytan Ruppin, Yosef Yarden
Summary: EGFR inhibitors activate endogenous mutators in lung cancer cells, leading to drug resistance. Inhibiting this process can prevent drug resistance.
Article
Cell Biology
Soma Ghosh, Nishanth Belugali Nataraj, Ashish Noronha, Sushant Patkar, Arunachalam Sekar, Saptapama Mukherjee, Sabina Winograd-Katz, Lior Kramarski, Aakanksha Verma, Moshit Lindzen, Diana Drago Garcia, Joseph Green, Galit Eisenberg, Hava Gil-Henn, Arkaprabha Basu, Yan Lender, Shimon Weiss, Moshe Oren, Michal Lotem, Benjamin Geiger, Eytan Ruppin, Yosef Yarden
Summary: The research indicates that tumors with EGFR mutations have a lower response to immunotherapy, the EGFR pathway is associated with high PD-L1 expression and can promote an aggressive phenotype, while anti-PD-L1 antibodies can inhibit PD-L1 functions.
Article
Medicine, Research & Experimental
Maicol Mancini, Hilah Gal, Nadege Gaborit, Luigi Mazzeo, Donatella Romaniello, Tomer Meir Salame, Moshit Lindzen, Georg Mahlknecht, Yehoshua Enuka, Dominick G. A. Burton, Lee Roth, Ashish Noronha, Ilaria Marrocco, Dan Adreka, Raya Eilam Altstadter, Emilie Bousquet, Julian Downward, Antonio Maraver, Valery Krizhanovsky, Yosef Yarden
EMBO MOLECULAR MEDICINE
(2018)