Article
Multidisciplinary Sciences
Mingxi Yao, Ajay Tijore, Delfine Cheng, Jinyuan Vero Li, Anushya Hariharan, Boris Martinac, Guy Tran Van Nhieu, Charles D. Cox, Michael Sheetz
Summary: Mechanosensing is crucial for various physiological processes, and two major mechanosensing systems, focal adhesions and mechanosensitive ion channels, can convert mechanical features of the microenvironment into biochemical signals. Interestingly, it has been discovered that the mechanosensitive calcium-permeable channel Piezo1, previously thought to be diffusive on plasma membranes, binds to matrix adhesions in a force-dependent manner, thereby promoting cell spreading, adhesion dynamics, and calcium entry in normal cells but not in most cancer cells.
Article
Engineering, Biomedical
Duo Zhang, Yaqi Sheng, Nicholas Piano, Theresa Jakuszeit, Edward Jonathan Cozens, Lingqing Dong, Alexander K. Buell, Andreas Pollet, Iek Man Lei, Wenyu Wang, Eugene Terentjev, Yan Yan Shery Huang
Summary: Cell migration is regulated by the fibrillar structure of the extracellular matrix. Cells dynamically adjust their shape and migration trajectory in response to different fibrillar environments. The average step speed of cells is minimally affected by the global pattern of the fibers, but a switch in behavior is observed when the pattern features approach the upper limit of the cell body's minor axis.
Article
Engineering, Biomedical
Samuel Alkmin, Manish S. Patankar, Paul J. Campagnola
Summary: Ovarian cancer is the deadliest gynecological cancer due to poor screening and imaging tools as well as limited understanding of the tumor microenvironment. This study used multiphoton excited fabrication to create orthogonal models representing the collagen matrix morphology and stiffness of normal ovarian stroma and high grade serous ovarian cancers. The study found that fiber morphology and matrix stiffness play important roles in migration and cytoskeletal dynamics of normal and cancer cells, and cell-specific differences highlight the importance of presenting both morphology and stiffness cues.
ACTA BIOMATERIALIA
(2022)
Article
Biochemical Research Methods
Marco Ruscone, Arnau Montagud, Philippe Chavrier, Olivier Destaing, Isabelle Bonnet, Andrei Zinovyev, Emmanuel Barillot, Vincent Noël, Laurence Calzone
Summary: In this study, a multiscale model is used to investigate the invasion process of tumor cells. The model combines agent-based modeling and continuous time Markov processes applied on Boolean network models. By considering both spatial information from the agent-based simulation and intracellular regulation from the Boolean model, the model aims to study different modes of cell migration and predict means to block it. The multiscale model successfully reproduces single and collective migration processes and is validated on published experiments on cell invasion, suggesting possible targets to block invasive tumor phenotypes through in silico experiments.
Article
Multidisciplinary Sciences
Qi Xing, Mojtaba Parvizi, Manuela Lopera Higuita, Leigh G. Griffiths
Summary: The study found that human mesenchymal stem cells migrated faster on the serous surface than on the fibrous surface, potentially due to increased expression of integrin alpha (3) and alpha (11). Blockade of integrin alpha (3)beta (1) inhibited early hMSC migration on the serous side, while blockade of alpha (11)beta (1) inhibited later hMSC migration.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Asif Amin, Asif Lone, Faizah Farooq, Umer Majeed Wani, Fizallah Kawoosa, Raies A. A. Qadri
Summary: The interaction between Tetranectin and plasminogen is crucial for extracellular matrix degradation, enabling tumor cell invasion and metastasis. This study aimed to target the carbohydrate recognition domain (CRD) of Tetranectin using natural bioactive compounds to inhibit its interaction with the Kringle-4 domain of plasminogen. Diosgenin and scytonemin exhibited favorable interactions with CRD, but diosgenin showed increased stability in the CRD binding pocket compared to scytonemin. Diosgenin was found to exert a pronounced anti-proliferative effect on breast cancer cells and reduce their migration and invasiveness.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Florian Geiger, Lukas G. Schnitzler, Manuel S. Brugger, Christoph Westerhausen, Hanna Engelke
Summary: This study investigates the influence of fiber orientation on invasion from a cancer cell spheroid in a collagen matrix. The results demonstrate a strong preference for invasion along radial fibers rather than tangential fibers.
Article
Biochemical Research Methods
Qi Liu, Chih-Yuan Hsu, Jia Li, Yu Shyr
Summary: This study developed a statistical method for examining dysregulated ligand-receptor interactions in different conditions, and successfully applied it to the study of important diseases such as COVID-19 infection and pulmonary fibrosis.
Article
Pharmacology & Pharmacy
Ellen Emi Kato, Luciana Araujo Pimenta, Maira Estanislau Soares de Almeida, Vanessa Olzon Zambelli, Marinilce Fagundes dos Santos, Sandra Coccuzzo Sampaio
Summary: The study demonstrated that CTX inhibits major events involved in angiogenesis, such as tube formation and cell adhesion, proliferation, and migration. These actions were particularly effective against tumor stimuli, highlighting the importance of CTX's anti-angiogenic action in inhibiting tumor progression.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biology
Samantha C. Schwager, Katherine M. Young, Lauren A. Hapach, Caroline M. Carlson, Jenna A. Mosier, Tanner J. McArdle, Wenjun Wang, Curtis Schunk, Anissa L. Jayathilake, Madison E. Bates, Francois Bordeleau, Marc A. Antonyak, Richard A. Cerione, Cynthia A. Reinhart-King
Summary: Weakly migratory cancer cells disseminate from the primary tumor via communication with stromal cells and enhance cancer cell migration and metastasis by releasing microvesicles rich in Tg2.
Article
Cell Biology
Pedro Monteiro, David Remy, Eline Lemerle, Fiona Routet, Anne-Sophie Mace, Chloe Guedj, Benoit Ladoux, Stephane Vassilopoulos, Christophe Lamaze, Philippe Chavrier
Summary: This study reveals the unique distribution of caveolae and invadosomes along collagen fibrils, and the reciprocal interplay between these two structures in coordinating cell adhesion and extracellular matrix remodeling.
NATURE CELL BIOLOGY
(2023)
Article
Environmental Sciences
Ruijia Zhang, Jin Sun, Lanyin Tu, Wenhua Lu, Yizheng Li, Tiangang Luan, Baowei Chen
Summary: Tumor cell migration induced by arsenite (iAsIII) is associated with cancer progression. In human colorectal cancer (DLD-1) cells exposed to iAsIII, transcriptomics and metabolomics approaches reveal the interactive networks of functional genes and metabolites. The results show that iAsIII treatment leads to increased cell migration, activation of epithelial to mesenchymal transition (EMT), enhanced cell adhesion, matrix degradation through matrix metallopeptidases (MMPs), and interference with glutamine metabolism.
ENVIRONMENT INTERNATIONAL
(2023)
Article
Oncology
Stephane Chabaud, Eve Pellerin, Christophe Caneparo, Cassandra Ringuette-Goulet, Frederic Pouliot, Stephane Bolduc
Summary: The hypoxic condition during tumor growth has a significant impact on the survival and migration properties of bladder cancer cells. Low-grade bladder cancer cells tend to become more aggressive under hypoxic culture conditions, while high-grade cells tend to exhibit less aggressive characteristics. Hypoxia greatly alters the properties of bladder cancer cells, including matrix metalloproteinases expression and metabolic changes. Studying bladder cancer cells in hypoxic environments is vital for translating in vitro findings to an in vivo context.
Article
Multidisciplinary Sciences
Hui Sun, Yufeng Wang, Shentao Wang, Yikui Xie, Kun Sun, Shuai Li, Weitong Cui, Kai Wang
Summary: This article investigated the correlation between the expression patterns of collagen family genes and gastric cancer progression using bioinformatics analyses. It was found that many collagen family genes were overexpressed in gastric cancer tissues, especially in the early T stages, highlighting the significance of collagens in tumor enlargement of gastric cancer.
SCIENTIFIC REPORTS
(2023)
Review
Oncology
Jenna A. Mosier, Samantha C. Schwager, David A. Boyajian, Cynthia A. Reinhart-King
Summary: Metabolic reprogramming is a hallmark of cancer metastasis, where cancer cells adjust their metabolic pathways to meet the energetic demands of the tumor microenvironment. Mechanical and biochemical factors influence both cell migration and glucose metabolism in cancer cells. Understanding the metabolic plasticity of cancer cells can lead to the development of more effective clinical diagnostics and therapeutics.
CLINICAL & EXPERIMENTAL METASTASIS
(2021)
Article
Genetics & Heredity
Shivohum Bahuguna, Magda Atilano, Marcus Glittenberg, Dohun Lee, Srishti Arora, Lihui Wang, Jun Zhou, Siamak P. Redhai, Michael P. Boutros, Petros P. Ligoxygakis
Summary: The immune system of fruit flies recognizes gut bacteria and activates a metabolic pathway to regulate lipid breakdown, which is important for the retention of intestinal bacteria. The TOR pathway inhibits lipid breakdown in fly mutants with reduced immune recognition, leading to increased gut fat accumulation. Blocking the TOR pathway restores both lipid levels and the density of gut bacteria to normal levels.
Article
Biology
Giulia Ambrosi, Oksana Voloshanenko, Antonia F. Eckert, Dominique Kranz, G. Ulrich Nienhaus, Michael Boutros
Summary: Wnt signaling is important in various biological processes, and mutations in beta-catenin can activate this signaling pathway. In this study, fluorescently tagged alleles of wild-type and mutant beta-catenin were engineered and analyzed to understand their properties. The results revealed distinct biophysical properties between the two alleles, and the wild-type allele could be manipulated to mimic the properties of the mutant allele through specific treatments.
Article
Biology
Christopher J. Neufeldt, Berati Cerikan, Mirko Cortese, Jamie Frankish, Ji-Young Lee, Agnieszka Plociennikowska, Florian Heigwer, Vibhu Prasad, Sebastian Joecks, Sandy S. Burkart, David Y. Zander, Baskaran Subramanian, Rayomand Gimi, Seetharamaiyer Padmanabhan, Radhakrishnan Iyer, Mathieu Gendarme, Bachir El Debs, Niels Halama, Uta Merle, Michael Boutros, Marco Binder, Ralf Bartenschlager
Summary: SARS-CoV-2 infection can lead to severe symptoms and long-lasting lung damage or death. This is often associated with high levels of pro-inflammatory cytokines and low antiviral responses. A specific activation of NF-kappa B and block of IRF3 nuclear translocation were observed in infected cells. The inflammatory response is mediated by cGAS-STING activation and can be attenuated through STING-targeting drugs.
COMMUNICATIONS BIOLOGY
(2022)
Article
Oncology
Antonio Sorrentino, Ayse Nur Menevse, Tillmann Michels, Valentina Volpin, Franziska Christine Durst, Julian Sax, Maria Xydia, Abir Hussein, Slava Stamova, Steffen Spoerl, Nicole Heuschneider, Jasmin Muehlbauer, Katharina Marlene Jeltsch, Anchana Rathinasamy, Melanie Werner-Klein, Marco Breinig, Damian Mikietyn, Christian Kohler, Isabel Poschke, Sabrina Purr, Olivia Reidell, Catarina Martins Freire, Rienk Offringa, Claudia Gebhard, Rainer Spang, Michael Rehli, Michael Boutros, Christian Schmidl, Nisit Khandelwal, Philipp Beckhove
Summary: This study reveals a molecular mechanism that protects tumor cells from cytotoxic T-cell attack and demonstrates the feasibility of pharmacological inhibition of this pathway.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
A. Echle, N. Ghaffari Laleh, P. Quirke, H. Grabsch, H. S. Muti, O. L. Saldanha, S. F. Brockmoeller, P. A. van den Brandt, G. G. A. Hutchins, S. D. Richman, K. Horisberger, C. Galata, M. P. Ebert, M. Eckardt, M. Boutros, D. Horst, C. Reissfelder, E. Alwers, T. J. Brinker, R. Langer, J. C. A. Jenniskens, K. Offermans, W. Mueller, R. Gray, S. B. Gruber, J. K. Greenson, G. Rennert, J. D. Bonner, D. Schmolze, J. Chang-Claude, H. Brenner, C. Trautwein, P. Boor, D. Jaeger, N. T. Gaisa, M. Hoffmeister, N. P. West, J. N. Kather
Summary: This study developed an AI-based system to identify microsatellite instability/mismatch repair deficiency in colorectal cancer, achieving high accuracy. The system can be used to rule out MSI/dMMR, reducing the cost and time for molecular profiling.
Article
Oncology
Leonhard Valentin Bamberg, Florian Heigwer, Anna Maxi Wandmacher, Ambika Singh, Johannes Betge, Niklas Rindtorff, Johannes Werner, Julia Josten, Olga Valerievna Skabkina, Isabel Hinsenkamp, Gerrit Erdmann, Christoph Roecken, Matthias P. Ebert, Elke Burgermeister, Tianzuo Zhan, Michael Boutros
Summary: Epigenetic dysregulation plays an important role in colorectal cancer (CRC), and combining histone deacetylase (HDAC) inhibitors with Euchromatic Histone Lysine N-Methyltransferases 1 and 2 (EHMT1/2) inhibitors has shown promising results in reducing CRC growth. Low expression of EHMT2 protein is associated with advanced CRC and poor clinical outcomes. Cotargeting HDAC and EHMT1/2 synergistically reduces proliferation of CRC cell lines through mechanisms such as cell cycle arrest and modulation of autophagy. This combination therapy strategy also decreases tumor viability in advanced models of CRC.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Multidisciplinary Sciences
Antonia Schubert, Oksana Voloshanenko, Franziska Ragaller, Philipp Gmach, Dominique Kranz, Christian Scheeder, Thilo Miersch, Matthias Schulz, Lorenz Truemper, Claudia Binder, Marko Lampe, Ulrike Engel, Michael Boutros
Summary: Dishevelled proteins play a crucial role in Wnt signaling pathways, and their formation of supramolecular condensates is coordinated dynamically and dependent on cellular state and Wnt signaling levels.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Johannes Betge, Niklas Rindtorff, Jan Sauer, Benedikt Rauscher, Clara Dingert, Haristi Gaitantzi, Frank Herweck, Kauthar Srour-Mhanna, Thilo Miersch, Erica Valentini, Kim E. Boonekamp, Veronika Hauber, Tobias Gutting, Larissa Frank, Sebastian Belle, Timo Gaiser, Inga Buchholz, Ralf Jesenofsky, Nicolai Haertel, Tianzuo Zhan, Bernd Fischer, Katja Breitkopf-Heinlein, Elke Burgermeister, Matthias P. Ebert, Michael Boutros
Summary: Patient-derived organoids can be used to model human diseases and tumors, and understanding their morphology can provide insights into treatment response. This study uses high-throughput imaging analysis to quantify the phenotypes of colorectal cancer organoids after treatment with small molecules, and identifies the underlying biological mechanisms and drug interventions that can influence their morphology.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Oncology
Eric Solary, Patricia Blanc, Michael Boutros, Charis Girvalaki, Franco Locatelli, Rene H. Medema, Peter Nagy, Josep Tabernero
Summary: UNCAN.eu is a European initiative aimed at advancing cancer research through the creation of a research data hub, leading to new developments in cancer care.
Article
Biochemistry & Molecular Biology
Anna Mendaluk, Emmanuel Caussinus, Michael Boutros, Christian F. Lehner
Summary: A change in ambient temperature affects cellular processes non-uniformly, with enzymes being more sensitive than diffusion. The molecular-level effects of temperature variation on cells are still poorly understood. A genome-wide RNA interference screen identified genes with physiological significance at different temperatures. Validation experiments confirmed the importance of the gene ballchen at lower temperatures.
Review
Developmental Biology
Lucie Wolf, Michael Boutros
Summary: Intercellular communication by Wnt proteins is crucial for development, tissue homeostasis, and disease. The secretion of Wnt proteins depends on Evi/Wntless and Porcupine, which are transmembrane proteins. This review summarizes the transportation of Wnt proteins from the ER to the plasma membrane, the role of SNX3-retromer in this process, the regulation of Wnt secretion, and the importance of Wnt secretion in organ development and cancer.
Review
Biochemistry & Molecular Biology
Johannes Werner, Kim E. Boonekamp, Tianzuo Zhan, Michael Boutros
Summary: Wnt ligands are secreted signaling proteins with a wide range of biological effects. Dysregulation of Wnt signaling is associated with cancer, and genetic alterations result in pathway hyperactivation. Recent research focuses on the interaction of Wnt signaling with tumor micro-environment. The review outlines the function of Wnt ligands in different tumors and their impact on key phenotypes, as well as approaches to target them in cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Michael Baumann, Julio Celis, Ulrik Ringborg, Manuel Heitor, Anton Berns, Tit Albreht, Jeliazko Arabadjiev, Michael Boutros, Mario Brandenburg, Helena Canhao, Fatima Carneiro, Christine Chomienne, Francesco De Lorenzo, Alexander M. M. Eggermont, Angel Font, Elena Garralda, Margarida Goulart, Rui Henrique, Mark Lawler, Lena Maier-Hein, Francoise Meunier, Simon Oberst, Pedro Oliveira, Maria Papatriantafyllou, Joachim Schuez, Eric Solary, Alfonso Valencia, Rosalia Vargas, Elisabete Weiderpass, Nils Wilking
Summary: European cancer research stakeholders gathered in Heidelberg, Germany, for the 5(th) Gago conference on European Cancer Policy in October 2022. The meeting focused on the current state of cancer research and care policy in Europe, identifying gaps in existing programs and proposing priorities for the future through the Heidelberg Manifesto for cancer research. The discussions in the meeting covered various aspects of cancer research, including infrastructure, digitalization, and collaboration, with an emphasis on implementation and sustainability.
MOLECULAR ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sara Kassel, Alison J. Hanson, Hassina Benchabane, Kenyi Saito-Diaz, Carly R. Cabel, Lily Goldsmith, Muhammad Taha, Aksheta Kanuganti, Victoria H. Ng, George Xu, Fei Ye, Julia Picker, Fillip Port, Michael Boutros, Vivian L. Weiss, David J. Robbins, Curtis A. Thorne, Yashi Ahmed, Ethan Lee
Summary: The Wnt-beta-catenin signal transduction pathway is crucial for embryonic development and adult tissue homeostasis. The deubiquitylase USP47 has been identified as a positive regulator of Wnt signaling by counteracting the E3 ligase activity of XIAP on the transcriptional corepressor Groucho/TLE. This mechanism helps to ensure that the expression of Wnt target genes continues only as long as the upstream signal is present.
Article
Biochemistry & Molecular Biology
Florian Heigwer, Christian Scheeder, Josephine Bageritz, Schayan Yousefian, Benedikt Rauscher, Christina Laufer, Sergi Beneyto-Calabuig, Maja Christina Funk, Vera Peters, Maria Boulougouri, Jana Bilanovic, Thilo Miersch, Barbara Schmitt, Claudia Blass, Fillip Port, Michael Boutros
Summary: This article reports a study that utilizes synthetic genetic interaction and cell morphology data to investigate gene function. They used machine learning to assign functions to genes in 47 modules and identified an interaction between Cdk2 and the Cop9 signalosome complex. These data provide a genome-scale resource for uncovering the mechanisms underlying genetic interactions and their plasticity at the single-cell level.