Article
Biology
Sepideh Fallah, Jean-Francois Beaulieu
Summary: This study reveals the regulatory mechanism of YAP1 in intestinal cell differentiation and demonstrates the impact of SFKs on YAP1 expression and intestinal cell specific gene expression. The results suggest that YAP1 and TAZ are not always interchangeable in regulating cell functions.
Article
Immunology
Nikolaos Koutras, Vasileios Morfos, Kyriakos Konnaris, Adamantia Kouvela, Athanasios-Nasir Shaukat, Constantinos Stathopoulos, Vassiliki Stamatopoulou, Konstantina Nika
Summary: This study reveals the ectopic function of SFKs in B cells and compares it to the predominant B cell SFK, Lyn. Our findings show substrate promiscuity displayed by these two SFKs, which is regulated by different mechanisms. Moreover, we demonstrate that signals generated by Lck and Lyn are sufficient to induce transcriptome alterations in B cells, resembling B cell activation. Additionally, we uncover a previously unknown role of SFKs in tipping the balance of cellular stress responses in B lymphocytes.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell Biology
Maria A. Ortiz, Tatiana Mikhailova, Xiang Li, Baylee A. Porter, Alaji Bah, Leszek Kotula
Summary: Despite over a century of scientific inquiry since the discovery of v-SRC, there is still no final judgement on SRC function. However, Src family kinases have been defined as key players in tumor progression, invasion and metastasis. Understanding the role of SFKs in mediating invasion and metastasis processes has grown along with the evidence supporting epithelial-mesenchymal transition (EMT) in these processes. This article describes key mechanisms through which SFKs play critical roles in epithelial homeostasis and propagate invasive signals.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Chemistry, Analytical
Ge Ge, Yanrong Wen, Pengfei Li, Zhanchen Guo, Zhen Liu
Summary: Cell migration is a crucial process in cancer metastasis, and the dynamics of ABL1 kinase have been found to affect cell migration speed. In this study, a unique single-cell analysis method was developed to observe the shuttling dynamics of ABL1 and its impact on cell migration. The results showed that ABL1 shuttling to the cytoplasm increased migration speed, while its trafficking back to the nucleus decreased speed. Fluctuant protein-protein interactions between 14-3-3 and ABL1 were also found to modulate ABL1's nucleocytoplasmic fluctuation and cell speed.
ANALYTICAL CHEMISTRY
(2023)
Article
Cell Biology
Yash Chhabra, Pernille Seiffert, Rachel S. Gormal, Manon Vullings, Christine Mei Mei Lee, Tristan P. Wallis, Farhad Dehkhoda, Sowmya Indrakumar, Nina L. Jacobsen, Kresten Lindorff-Larsen, Nela Durisic, Michael J. Waters, Frederic A. Meunier, Birthe B. Kragelund, Andrew J. Brooks
Summary: Growth hormone (GH) regulates growth, metabolism, and neural function through JAK2 and LYN tyrosine kinases. Our interdisciplinary study reveals competition between JAK2 and LYN for GH receptor (GHR) binding and identifies the role of LYN in GHR nanoclustering, signaling, and degradation. This study provides insights into the molecular interactions of LYN and GHR and sheds light on the functions of LYN in cytokine receptor regulation.
Review
Biochemistry & Molecular Biology
Nannan Li, Guoxin Lin, Hao Zhang, Jian Sun, Ming Gui, Yan Liu, Wei Li, Jishi Liu, Juan Tang
Summary: Src family kinases (SFKs) have been found to play a crucial role in acute kidney injury (AKI), making them potential therapeutic targets.
Article
Oncology
Ishwar N. Kohale, Jia Yu, Yongxian Zhuang, Xiaoyang Fan, Raven J. Reddy, Jason Sinnwell, Krishna R. Kalari, Judy C. Boughey, Jodi M. Carter, Matthew P. Goetz, Liewei Wang, Forest M. White
Summary: Breast cancer is the leading cause of cancer-related deaths in women globally, with triple negative breast cancer (TNBC) known for being highly aggressive and resistant to chemotherapy. In this study, the researchers identified Src family kinases (SFKs) as potential drug targets for chemotherapy-resistant TNBC. However, the prevalence of SFK-driven tumors was found to be low in human tumor tissue specimens. These findings highlight the importance of characterizing phosphotyrosine signaling profiles for patient stratification and therapeutic options.
Article
Neurosciences
Dandan Wang, Brian W. Howell, Eric C. Olson
Summary: The study found that alcohol exposure can induce tyrosine phosphorylation response in the fetal brain, affecting cortical development. This initial phosphorylation response activated by alcohol has the potential to disrupt multiple developmentally important signaling systems.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Neurosciences
Han Qiu, Tianyang Qian, Tong Wu, Ting Gao, Qinghe Xing, Laishuan Wang
Summary: This study identified the pattern of p-Src expression after HI brain injury in immature rats and demonstrated its relationship with activated NMDA receptors. Inhibiting p-Src can ameliorate neuropathological changes and damage to neurological functions induced by HI injury.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Biochemical Research Methods
Guido Domingo, Milena Marsoni, Luca Chiodaroli, Stefania Fortunato, Marcella Bracale, Maria Concetta De Pinto, Chris Gehring, Candida Vannini
Summary: 3',5'-cyclic adenosine monophosphate (cAMP) is recognized as a crucial signaling molecule in plants, and its role in cellular processes such as hormone response and environmental stimuli has been studied. A phosphoproteomic analysis of tobacco BY-2 cells with modulated cAMP levels revealed the significant impact of cAMP on plant kinome, mRNA processing, and cellular programming. The findings suggest the importance of unperturbed cellular cAMP levels for plant cellular homeostasis and signaling.
Article
Multidisciplinary Sciences
Junchen Tang, Weichao Li, Tzu-Yuan Chiu, Francisco Martinez-Pena, Zengwei Luo, Christine T. Chong, Qijia Wei, Nathalia Gazaniga, Thomas J. West, Yi Yang See, Luke L. Lairson, Christopher G. Parker, Phil S. Baran
Summary: A scalable and concise synthesis of portimines has been successfully achieved, allowing for the structural reassignment of portimine B and in-depth functional evaluation of portimine A. The results demonstrate that portimine A has the ability to selectively induce apoptosis in human cancer cells with high potency and is efficacious in tumor clearance models in vivo.
Review
Cell Biology
Xianzheng Zhang, Dan Mei, Lingling Zhang, Wei Wei
Summary: Autoimmune diseases encompass a spectrum of over 80 known disorders, with B cells playing a critical role in their development. Src family protein kinases (SFKs), including LYN, BLK, and Fyn, are important regulators in B lymphocytes, impacting the risk and progression of autoimmune disorders. Understanding the functions of these SFKs in autoimmune diseases could provide valuable insights for future therapeutic strategies.
Article
Clinical Neurology
Lingdi Nie, Dongqing Ma, John P. Quinn, Minyan Wang
Summary: This study reveals that SFKs activity transmits P2X7 receptor signaling to facilitate CSD propagation via the glutamatergic pathway and promote neuroinflammation, which is particularly relevant to migraine.
JOURNAL OF HEADACHE AND PAIN
(2021)
Article
Biochemistry & Molecular Biology
Dingjin Yao, Yiran Deng, Si Zhang, Limiao Liang, Li Zhang, Shuqiang Weng, She Chen
Summary: This study aimed to thoroughly investigate the mutation status, expression level, prognostic value and relationship of Src family kinases (SFKs) in hepatocellular carcinoma (HCC). The study found that elevated mRNA expression levels of LYN, SRC, and SRM were observed in HCC tissues, whereas FYN was reduced. Approximately 10% genetic alterations rate of SFKs was observed in HCC. Dysregulated FYN and SRC expression in HCC were associated with poor prognosis and may be used as novel prognostic biomarkers in patients with HCC.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2023)
Article
Medicine, General & Internal
Adaikalasamy Premanand, Baskaran Reena Rajkumari
Summary: This study identified key genes and pathways involved in premature androgenetic alopecia (AGA) through analysis of gene expression data. The results showed that genes related to immune systems, cytokine signaling, and interferon signaling pathways were up-regulated, while genes involved in skin epidermis structure formation, hair follicle development, and hair cycle were down-regulated in the scalp of AGA patients. Network analysis identified 25 hub genes that play crucial roles in AGA pathogenesis. The study also highlighted the potential therapeutic targets of tyrosine kinase genes LCK and LYN in the inflammatory process in AGA.
FRONTIERS IN MEDICINE
(2023)
Article
Genetics & Heredity
Andrey V. Marakhonov, Magdalena Prechova, Fedor A. Konovalov, Alexandra Yu. Filatova, Maria A. Zamkova, Ilya V. Kanivets, Vladimir G. Solonichenko, Natalia A. Semenova, Rena A. Zinchenko, Richard Treisman, Mikhail Yu. Skoblov
Summary: A novel rare genetic mutation associated with severe multifocal epilepsy in a patient was discovered in this study. The mutation decreased the affinity of the PHACTR1 protein for G-actin, leading to increased binding tendency with the catalytic subunit of PP1. These alterations may cause abnormal cytoskeletal rearrangements, ultimately triggering epilepsy symptoms.
Article
Cell Biology
Hiroshi Kondo, Colin D. H. Ratcliffe, Steven Hooper, James Ellis, James MacRae, Marc Hennequart, Christopher W. Dunsby, Kurt Anderson, Erik Sahai
Summary: The study tracks the transition and heritability of metabolic states in single PIK3CA mutant breast cancer cells, identifying non-genetic glycolytic heterogeneity. It reveals distinct subpopulations of cells with regulated glycolytic and mitochondrial metabolism by PI3K signaling, bromodomain activity, and cell crowding effects, showing how targeting these pathways affects specific subpopulations of cancer cells.
Article
Cell & Tissue Engineering
Lucia Cordero-Espinoza, Anna M. Dowbaj, Timo N. Kohler, Bernhard Strauss, Olga Sarlidou, German Belenguer, Clare Pacini, Nuno P. Martins, Ross Dobie, John R. Wilson-Kanamori, Richard Butler, Nicole Prior, Palle Serup, Florian Jug, Neil C. Henderson, Florian Hollfelder, Meritxell Huch
Summary: This study demonstrates that a subpopulation of mouse periportal mesenchymal cells in organoid co-cultures exert dual control on epithelial proliferation, mediated by Notch signaling. Proliferation of ductal cells is influenced by the number of direct mesenchymal cell contacts, highlighting the critical role of cell-cell contacts in regulating cellular behaviors during regeneration.
Article
Genetics & Heredity
Satyamaanasa Polubothu, Davide Zecchin, Lara Al-Olabi, Daniel A. Lionarons, Mark Harland, Stuart Horswell, Anna C. Thomas, Lilian Hunt, Nathan Wlodarchak, Paula Aguilera, Sarah Brand, Dale Bryant, Cristina Carrera, Hui Chen, Greg Elgar, Catherine A. Harwood, Michael Howell, Lionel Larue, Sam Loughlin, Jeff MacDonald, Josep Malvehy, Sara Martin Barberan, Vanessa Martins da Silva, Miriam Molina, Deborah Morrogh, Dale Moulding, Jeremie Nsengimana, Alan Pittman, Juan-Anton Puig-Butille, Kiran Parmar, Neil J. Sebire, Stephen Scherer, Paulina Stadnik, Philip Stanier, Gemma Tell, Regula Waelchli, Mehdi Zarrei, Susana Puig, Veronique Bataille, Yongna Xing, Eugene Healy, Gudrun E. Moore, Wei-Li Di, Julia Newton-Bishop, Julian Downward, Veronica A. Kinsler
Summary: This study identified a previously unreported genetic susceptibility to melanoma and melanocytic nevi, familial duplications of gene PPP2R3B. Duplications of this gene increase the expression of PR70 in human nevus and melanoma tissue, affecting survival through a nonimmunological mechanism. Overexpression of PPP2R3B induces pigment cell switching toward proliferation and away from migration, driven by C21orf91 independent of the known MITF-controlled switch. This work confirms the power of a rare disease approach and identifies C21orf91 as a potentially targetable hub in controlling phenotype switching.
GENETICS IN MEDICINE
(2021)
Article
Cell Biology
Anna M. Dowbaj, Robert P. Jenkins, Daniel Williamson, John M. Heddleston, Alessandro Ciccarelli, Todd Fallesen, Klaus M. Hahn, Reuben D. O'Dea, John R. King, Marco Montagner, Erik Sahai
Summary: The shuttle of transcription factors and transcriptional regulators is crucial for the regulation of biological processes. A new method involving optogenetic release of YAP1 and TAZ from sequestration demonstrates the correlation between their rates of entry and exit. Phosphorylation influences YAP1's rate of nuclear export, indicating a complex regulatory mechanism for protein dynamics.
JOURNAL OF CELL SCIENCE
(2021)
Letter
Medicine, General & Internal
Emma C. Wall, Mary Wu, Ruth Harvey, Gavin Kelly, Scott Warchal, Chelsea Sawyer, Rodney Daniels, Philip Hobson, Emine Hatipoglu, Yenting Ngai, Saira Hussain, Jerome Nicod, Robert Goldstone, Karen Ambrose, Steve Hindmarsh, Rupert Beale, Andrew Riddell, Steve Gamblin, Michael Howell, George Kassiotis, Vincenzo Libri, Bryan Williams, Charles Swanton, Sonia Gandhi, David L. V. Bauer
Letter
Medicine, General & Internal
Emma C. Wall, Mary Wu, Ruth Harvey, Gavin Kelly, Scott Warchal, Chelsea Sawyer, Rodney Daniels, Lorin Adams, Philip Hobson, Emine Hatipoglu, Yenting Ngai, Saira Hussain, Karen Ambrose, Steve Hindmarsh, Rupert Beale, Andrew Riddell, Steve Gamblin, Michael Howell, George Kassiotis, Vincenzo Libri, Bryan Williams, Charles Swanton, Sonia Gandhi, David L. V. Bauer
Article
Biology
Nikhil Faulkner, Kevin W. Ng, Mary Y. Wu, Ruth Harvey, Marios Margaritis, Stavroula Paraskevopoulou, Catherine Houlihan, Saira Hussain, Maria Greco, William Bolland, Scott Warchal, Judith Heaney, Hannah Rickman, Moria Spyer, Daniel Frampton, Matthew Byott, Tulio de Oliveira, Alex Sigal, Svend Kjaer, Charles Swanton, Sonia Gandhi, Rupert Beale, Steve J. Gamblin, John W. McCauley, Rodney Stuart Daniels, Michael Howell, David Bauer, Eleni Nastouli, George Kassiotis
Summary: The study found that antibodies elicited by infection with the B.1.1.7 variant exhibited significantly reduced recognition and neutralization of parental strains or the South Africa variant B.1.351, indicating an asymmetric heterotypic immunity induced by SARS-CoV-2 variants.
Article
Multidisciplinary Sciences
German Belenguer, Gianmarco Mastrogiovanni, Clare Pacini, Zoe Hall, Anna M. Dowbaj, Robert Arnes-Benito, Aleksandra Sljukic, Nicole Prior, Sofia Kakava, Charles R. Bradshaw, Susan Davies, Michele Vacca, Kourosh Saeb-Parsy, Bon-Kyoung Koo, Meritxell Huch
Summary: RNF43/ZNRF3 alterations contribute to liver disease and liver cancer by affecting differentiation and lipid metabolism of hepatocytes. The loss of these genes leads to steatohepatitis and an increase in unsaturated lipids. Deletion of Rnf43/Znrf3 results in defective hepatocyte regeneration and liver cancer, causing an imbalance between differentiation and proliferation. Interestingly, ZNRF3 mutant liver cancer patients have a poorer prognosis and exhibit altered hepatic lipid metabolism and steatohepatitis/NASH signatures.
NATURE COMMUNICATIONS
(2022)
Article
Infectious Diseases
Ana Atti, Ferdinando Insalata, Edward J. Carr, Ashley D. Otter, Javier Castillo-Olivares, Mary Wu, Ruth Harvey, Michael Howell, Andrew Chan, Jonathan Lyall, Nigel Temperton, Diego Cantoni, Kelly da Costa, Angalee Nadesalingam, Andrew Taylor-Kerr, Nipunadi Hettiarachchi, Caio Tranquillini, Jacqueline Hewson, Michelle J. Cole, Sarah Foulkes, Katie Munro, Edward J. M. Monk, Iain D. Milligan, Ezra Linley, Meera A. Chand, Colin S. Brown, Jasmin Islam, Amanda Semper, Andre Charlett, Jonathan L. Heeney, Rupert Beale, Maria Zambon, Susan Hopkins, Tim Brooks, Victoria Hall
Summary: This study investigated the serological differences between SARS-CoV-2 reinfection cases and controls, and identified antibody correlates of protection against reinfection. The results showed that before vaccination, protection against reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels.
JOURNAL OF INFECTION
(2022)
Article
Biology
Takuya Kato, Robert P. Jenkins, Stefanie Derzsi, Melda Tozluoglu, Antonio Rullan, Steven Hooper, Raphael A. G. Chaleil, Holly Joyce, Xiao Fu, Selvam Thavaraj, Paul A. Bates, Erik Sahai, Edna Cukierman
Summary: Cancers, such as squamous cell carcinoma, invade as multicellular units and the mode of invasion is determined by factors including matrix proteolysis and cell-cell junctions. Wide strands of invasion are formed through matrix proteolysis and cell-cell junctions, and efficient invasion also requires cell-cell junctions in response to uniform directional cues. The ability to generate wide invasive strands is linked to effective growth in a three-dimensional environment. The most aggressive cancer behavior is achieved at high levels of both cell-cell adhesion and matrix proteolysis, contrary to expectations.
Article
Biochemical Research Methods
Anna M. Dowbaj, Timo N. Kohler, Lucia Cordero-Espinoza, Florian Hollfelder, Meritxell Huch
Summary: This study provides two co-culture techniques to incorporate liver portal mesenchyme into ductal cell organoids, which mimic their cellular interactions in vitro. The protocol can be easily adapted to cells from other organs.
Article
Multidisciplinary Sciences
Jordan Whisler, Somayeh Shahreza, Karin Schlegelmilch, Nil Ege, Yousef Javanmardi, Andrea Malandrino, Ayushi Agrawal, Alessandro Fantin, Bianca Serwinski, Hesham Azizgolshani, Clara Park, Victoria Shone, Olukunle O. Demuren, Amanda Del Rosario, Vincent L. Butty, Natalie Holroyd, Marie-Charlotte Domart, Steven Hooper, Nicolas Szita, Laurie A. Boyer, Simon Walker-Samuel, Boris Djordjevic, Graham K. Sheridan, Lucy Collinson, Fernando Calvo, Christiana Ruhrberg, Erik Sahai, Roger Kamm, Emad Moeendarbary
Summary: Vascularization is driven by morphogen signals and mechanical cues that regulate cellular force generation, migration, and shape change. The developing vasculature actively regulates its own mechanical properties to achieve effective vascularization. Tissue stiffness increases during vascular morphogenesis resulting from interactions between endothelial cells, fibroblasts, and ECM, and correlates with enhanced vascular function. Contractile cellular forces, synergizing with ECM mechanical properties and mediated by YAP1, play a key role in emergent tissue stiffening and vascular function. Mouse embryos lacking YAP1 in fibroblasts exhibit reduced tissue stiffness and lethal vascular defects. Translating these findings through biology-inspired vascular tissue engineering approaches will have substantial implications in regenerative medicine.
Article
Oncology
Annika Fendler, Scott T. C. Shepherd, Lewis Au, Katalin A. Wilkinson, Mary Wu, Fiona Byrne, Maddalena Cerrone, Andreas M. Schmitt, Nalinie Joharatnam-Hogan, Benjamin Shum, Zayd Tippu, Karolina Rzeniewicz, Laura Amanda Boos, Ruth Harvey, Eleanor Carlyle, Kim Edmonds, Lyra Del Rosario, Sarah Sarker, Karla Lingard, Mary Mangwende, Lucy Holt, Hamid Ahmod, Justine Korteweg, Tara Foley, Jessica Bazin, William Gordon, Taja Barber, Andrea Emslie-Henry, Wenyi Xie, Camille L. Gerard, Daqi Deng, Emma C. Wall, Ana Agua-Doce, Sina Namjou, Simon Caidan, Mike Gavrielides, James MacRae, Gavin Kelly, Kema Peat, Denise Kelly, Aida Murra, Kayleigh Kelly, Molly O'Flaherty, Lauren Dowdie, Natalie Ash, Firza Gronthoud, Robyn L. Shea, Gail Gardner, Darren Murray, Fiona Kinnaird, Wanyuan Cui, Javier Pascual, Simon Rodney, Justin Mencel, Olivia Curtis, Clemency Stephenson, Anna Robinson, Bhavna Oza, Sheima Farag, Isla Leslie, Aljosja Rogiers, Sunil Iyengar, Mark Ethell, Christina Messiou, David Cunningham, Ian Chau, Naureen Starling, Nicholas Turner, Liam Welsh, Nicholas van As, Robin L. Jones, Joanne Droney, Susana Banerjee, Kate C. Tatham, Mary O'Brien, Kevin Harrington, Shreerang Bhide, Alicia Okines, Alison Reid, Kate Young, Andrew J. S. Furness, Lisa Pickering, Charles Swanton, Sonia Gandhi, Steve Gamblin, David L. Bauer, George Kassiotis, Sacheen Kumar, Nadia Yousaf, Shaman Jhanji, Emma Nicholson, Michael Howell, Susanna Walker, Robert J. Wilkinson, James Larkin, Samra Turajlic
Summary: A cohort study evaluated 585 cancer patients following vaccination with BNT162b2 or AZD1222 vaccines, finding lower antibody responses in patients with hematological malignancies compared to those with solid tumors. Patients with hematological malignancies also had reduced neutralizing antibody responses compared to individuals without cancer. The study highlights the importance of managing cancer patients during the ongoing COVID-19 pandemic.
Review
Biochemistry & Molecular Biology
Nil Ege, Habib Bouguenina, Marianthi Tatari, Rajesh Chopra
Summary: This review provides a detailed summary of recent advances in understanding the mechanism of action of emerging protein degradation therapies, focusing on the use of phenotypic screening and chemical properties for drug discovery. By defining rules for selecting neo-substrates for degradation and exploring alternative E3 ligases, researchers are making significant progress in this field.
CELL CHEMICAL BIOLOGY
(2021)
