Article
Cell Biology
Pan Wang, Lu Zhao, Sheng Gong, Shuanglong Xiong, Junwei Wang, Dewei Zou, Jinyu Pan, Yangmin Deng, Qian Yan, Nan Wu, Bin Liao
Summary: HIF1α and HIF2α regulate each other with a negative feedback loop, affecting GBM malignant progression through the EGFR-PI3K/AKT pathway and increasing sensitivity to chemotherapy. Their interaction with Sox2 and Klf4 further contributes to stemness expression and cell cycle arrest, enhancing malignancy in GBM.
CELL DEATH & DISEASE
(2021)
Article
Chemistry, Medicinal
Nattamon Hongwiangchan, Nicharat Sriratanasak, Duangdao Wichadakul, Nithikoon Aksorn, Supakarn Chamni, Pithi Chanvorachote
Summary: CIN-RM has been shown to suppress lung cancer stem cells by inhibiting their colony and tumor spheroid formation. It also affects central survival and stem cell regulatory proteins, leading to the depletion of CSC markers. The compound's mechanism of action involves inhibiting Akt/mTOR signaling and promoting c-Myc degradation.
Article
Cell Biology
Jerry Hung-Hao Lo, Miguel Edwards, Justin Langerman, Rupa Sridharan, Kathrin Plath, Stephen T. Smale
Summary: By examining dynamic ranges of gene expression, the authors found that Oct4 and Sox2 binding is enriched near genes with large dynamic ranges of expression. Their results suggest that Oct4 and Sox2 directly establish both active and silent transcriptional states in pluripotent cells at a large number of genes subject to dynamic regulation.
GENES & DEVELOPMENT
(2022)
Review
Genetics & Heredity
Marisol Aguirre, Manuela Escobar, Sebastian Forero Amezquita, David Cubillos, Camilo Rincon, Paula Vanegas, Maria Paula Tarazona, Sofia Atuesta Escobar, Juan Camilo Blanco, Luis Gustavo Celis
Summary: The transcription factors Oct4, Sox2, Klf4, and c-Myc enable the reprogramming of somatic cells into induced pluripotent cells, with potential applications in cancer and neurodegenerative disease therapies. However, there are limitations and risks that require further investigation before their use in humans.
Article
Biochemistry & Molecular Biology
Li Kang, Huifang Zhang, Yaling Wang, Manyu Chu, Jianzhong He, Mengyang Xue, Liu Pan, Yunfeng Zhang, Zhen Wang, Zhaosu Chen, Yuanyong Huang, Zitai Chen, Enmin Li, Jiwen Li, Liyan Xu, Rong Zhang, Jiemin Wong
Summary: This study identifies HSP90 inhibitors as potential therapeutic agents for SOX2-positive cancers by regulating CHIP nuclear exclusion and HSP90 activity to suppress SOX2 protein stability and tumorigenic activity.
Article
Biochemistry & Molecular Biology
Lucas Simoes Machado, Camila Martins Borges, Marina Amaro de Lima, Juliano Rodrigues Sangalli, Jacinthe Therrien, Lais Vicari de Figueiredo Pessoa, Paulo Fantinato Neto, Felipe Perecin, Lawrence Charles Smith, Flavio Vieira Meirelles, Fabiana Fernandes Bressan
Summary: Mechanisms of cell reprogramming by pluripotency-related transcription factors or nuclear transfer seem to be mediated by similar pathways. The study suggests that OCT4 and SOX2 may contribute to both processes and help elucidate the mechanisms responsible for pluripotency.
Article
Cell & Tissue Engineering
Lan Zhao, Jianshuo Wang, Pengzhen Wang, Zhanyu Deng, Jin Cui, Weiguang Huang, Shaoheng Zhang
Summary: Cardiac-resident mesenchymal stem cells (cMSCs) can undergo mesenchymal-to-endothelial transition (MEndoT) with the cooperation of Oct4 and c-Myc, promoting angiogenesis and enhancing myocardial repair.
STEM CELL RESEARCH & THERAPY
(2022)
Review
Cell Biology
Wei Fan, Xiaoling Li
Summary: SIRT1 is a crucial NAD(+)-dependent protein deacetylase in mammals, involved in the metabolic and epigenetic regulation of stem cells through deacetylation of transcriptional factors and co-factors. It forms a positive feedback loop with c-Myc, which is important in tumorigenesis. Recent research has uncovered the significance of the SIRT1-c-Myc axis in the regulation of maintenance and differentiation of various stem cells. This review highlights the recent advances in understanding the role of the SIRT1-c-Myc axis in stem cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Peng Ye, Xiaoxia Chi, Xiuwen Yan, Fangqin Wu, Zhigang Liang, Wen-Hao Yang
Summary: This study reveals the crucial role of alanine-glyoxylate aminotransferase (AGXT) in supporting liver cancer stem cells (LCSCs) and maintaining their stemness. AGXT may sustain the self-renewal potential of LCSCs by upregulating the expression of SRY-box transcription factor 2 (SOX2) and octamer-binding transcription factor 4 (OCT4).
Article
Oncology
Ethan P. Metz, Phillip J. Wilder, Tessa M. Popay, Jing Wang, Qi Liu, Achyuth Kalluchi, M. Jordan Rowley, William P. Tansey, Angie Rizzino
Summary: Slowly cycling/infrequently proliferating tumor cells present a clinical challenge as they can evade treatment. Previous studies have shown that high levels of SOX2 restrict cell proliferation and induce a slowly cycling state in both fetal and tumor cells. However, the mechanisms through which elevated SOX2 levels inhibit tumor cell proliferation have not been identified. This study aimed to identify common mechanisms through which SOX2 elevation restricts tumor cell proliferation. The results showed that elevating SOX2 decreases the expression of MYC and MYC target genes. It was also discovered that the downregulation of MYC is a critical step in maintaining survival in the slowly cycling state induced by elevated SOX2. Overall, this study uncovers a novel SOX2:MYC signaling axis and provides important insights into the molecular mechanisms through which SOX2 elevation induces a slowly cycling proliferative state.
Article
Multidisciplinary Sciences
Marzena Swiderska-Syn, Julia Mir-Pedrol, Alexander Oles, Olga Schleuger, April D. Salvador, Sean M. Greiner, Cara Seward, Fan Yang, Benjamin R. Babcock, Chen Shen, Daniel T. Wynn, Avencia Sanchez-Mejias, Timothy R. Gershon, Vanesa Martin, Heather J. McCrea, Kathryn G. Lindsey, Carsten Krieg, Jezabel Rodriguez-Blanco
Summary: Single-cell transcriptomic analysis of medulloblastoma revealed that vismodegib treatment increased Sox2-expressing astrocyte-like cells. These Sox2(+) cells relied on Sonic Hedgehog (SHH) signaling, with MYC-dependent activation downstream of Smo. GLI inhibitors depleted resistant Sox2(+) cells, reduced their engraftment ability, and increased symptom-free survival.
Article
Biology
Yaguang Zhang, Xiaowen Wan, Lei Qiu, Lian Zhou, Qing Huang, Mingtian Wei, Xueqin Liu, Sicheng Liu, Bo Zhang, Junhong Han
Summary: This study investigates the citrullination of Trim28 in embryonic stem cells (ESCs) and its role in pluripotency regulation. The results demonstrate that citrullination of Trim28 enhances its interaction with Smarcad1, preventing chromatin condensation. Additionally, citrullinated Trim28 promotes the transcription of pluripotency genes Nanog and Klf4, thus maintaining the pluripotency of ESCs.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Editorial Material
Cell Biology
Ellen V. Rothenberg
Summary: Transcription factors bind to DNA in a sequence-specific manner and selectively impact gene expression, but their binding sites do not accurately predict the genes they directly control. A new study demonstrates that the same transcription factor binding sites have a greater impact on gene regulation during developmental change.
GENES & DEVELOPMENT
(2022)
Article
Cell Biology
Prakash P. Praharaj, Srimanta Patra, Soumya R. Mishra, Subhadip Mukhopadhyay, Daniel J. Klionsky, Shankargouda Patil, Sujit K. Bhutia
Summary: This study found that cisplatin treatment activated higher mitophagy in oral cancer stem cells by regulating CLU levels. CLU regulated mitochondrial fission by activating AKT kinase, leading to mitochondrial fission. Furthermore, CLU-mediated mitophagy positively regulated oral cancer stem cells by degrading MSX2 and preventing its nuclear translocation, which suppressed SOX2 activity and inhibited cancer stemness and self-renewal ability.
Article
Cell Biology
Md Mahfuz Al Mamun, Muhammad Riaz Khan, Yifu Zhu, Yuwei Zhang, Shuai Zhou, Ran Xu, Ihtisham Bukhari, Rick F. Thorne, Jinming Li, Xu Dong Zhang, Guangzhi Liu, Song Chen, Mian Wu, Xiaoyuan Song
Summary: This study identifies the E3 ubiquitin ligase Stub1 as a negative regulator of pluripotency in embryonic stem cells (ESCs). Stub1 catalyzes the degradation of Sox2, Oct4, and Nanog proteins, thereby reducing pluripotency. Deficiency of Stub1 enhances somatic cell reprogramming and delays differentiation, while its overexpression triggers ESC differentiation.
Article
Oncology
Clemens Messerschmidt, Benedikt Obermayer, Konrad Klinghammer, Sebastian Ochsenreither, Denise Treue, Albrecht Stenzinger, Hanno Glimm, Stefan Froehling, Thomas Kindler, Christian H. Brandts, Klaus Schulze-Osthoff, Wilko Weichert, Ingeborg Tinhofer, Frederick Klauschen, Ulrich Keilholz, Dieter Beule, Damian T. Rieke
INTERNATIONAL JOURNAL OF CANCER
(2020)
Article
Cell Biology
Franziska Wandrer, Stephanie Liebig, Silke Marhenke, Arndt Vogel, Katharina John, Michael P. Manns, Andreas Teufel, Timo Itzel, Thomas Longerich, Olaf Maier, Roman Fischer, Roland E. Kontermann, Klaus Pfizenmaier, Klaus Schulze-Osthoff, Heike Bantel
CELL DEATH & DISEASE
(2020)
Article
Hematology
Hannes Schmid, Emmanuelle M. Ribeiro, Kathy-Ann Secker, Silke Duerr-Stoerzer, Hildegard Keppeler, Ruoyun Dong, Timo Munz, Klaus Schulze-Osthoff, Stephan Hailfinger, Corina Schneidawind, Dominik Schneidawind
Summary: This study found that dendritic cells (DC) in the blood of patients with graft-versus-host disease (GvHD) play a crucial role in activating and proliferating T cells. Conversely, transferred iNKT cells inhibit allogeneic reactions of T cells by inducing apoptosis in specific subsets of DC, promoting beneficial immune responses.
Article
Immunology
Lena Michaelis, Marcel Tress, Hanna-Christine Loew, Johanna Klees, Christian Klameth, Anna Lange, Anne Griesshammer, Andrea Schaefer, Sarah Menz, Alex Steimle, Klaus Schulze-Osthoff, Julia-Stefanie Frick
Summary: Intestinal commensal bacteria play a significant role in regulating the development of Th17 cells, with potential implications for autoimmune diseases. The atypical nuclear I kappa B protein I kappa B zeta may be involved in this process. Different gut commensals with varying immunogenicity levels can affect the expression of I kappa B zeta in dendritic cells and influence the immune response, indicating potential therapeutic implications for autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
Anja Schmitt, Wendan Xu, Philip Bucher, Melanie Grimm, Martina Konantz, Heike Horn, Myroslav Zapukhlyak, Philipp Berning, Marc Braendle, Mohamed-Ali Jarboui, Caroline Sch Onfeld, Karsten Boldt, Andreas Rosenwald, German Ott, Michael Grau, Pavel Klener, Petra Vockova, Claudia Lengerke, Georg Lenz, Klaus Schulze-Osthoff, Stephan Hailfinger
Summary: The study demonstrates the broad antitumor effect of dimethyl fumarate (DMF) on both subtypes of DLBCL by inducing ferroptosis, especially in GCB DLBCL. In ABC DLBCL cells, DMF treatment efficiently inhibits the activity of the IKK complex and Janus kinases. Additionally, the combination of BCL-2-specific BH3 mimetic ABT-199 and an inhibitor of ferroptosis suppressor protein 1 synergize with DMF in inducing cell death in DLBCL.
Review
Biochemistry & Molecular Biology
Stephan Hailfinger, Klaus Schulze-Osthoff
Summary: Psoriasis is a common autoimmune-related skin disease that involves various cell types. Mutations in genes such as CARD14 can contribute to the development of the disease. The activation of MALT1, a key signaling molecule, plays a significant role in psoriasis by activating transcription factors and mediating disease progression through its protease activity and molecular scaffold function.
BIOLOGICAL CHEMISTRY
(2021)
Article
Dermatology
Stephan Hailfinger, Klaus Schulze-Osthoff
Summary: Dysfunctional autophagy is associated with inflammatory skin diseases such as psoriasis and atopic dermatitis. Stimulating autophagy may be a potential treatment option for these conditions. Impaired autophagy is linked to inflammation and disrupted keratinocyte differentiation in these diseases.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Cell Biology
Stephanie Busche, Katharina John, Franziska Wandrer, Florian W. R. Vondran, Ulrich Lehmann, Heiner Wedemeyer, Frank Essmann, Klaus Schulze-Osthoff, Heike Bantel
Summary: Anti-angiogenic immune checkpoint inhibitor-based combination therapy and tyrosine-kinase inhibitors like sorafenib are treatment options for hepatocellular carcinoma (HCC). However, response to these therapies can be enhanced by pro-apoptotic agents targeting specific BH3-only proteins. Individual profiling of BH3-only protein expression may help stratify patients for TKI-based HCC therapies.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Peter Horak, Christoph Heining, Simon Kreutzfeldt, Barbara Hutter, Andreas Mock, Jennifer Huellein, Martina Froehlich, Sebastian Uhrig, Arne Jahn, Andreas Rump, Laura Gieldon, Lino Moehrmann, Dorothea Hanf, Veronica Teleanu, Christoph E. Heilig, Daniel B. Lipka, Michael Allgaeuer, Leo Ruhnke, Andreas Lassmann, Volker Endris, Olaf Neumann, Roland Penzel, Katja Beck, Daniela Richter, Ulrike Winter, Stephan Wolf, Katrin Pfuetze, Christina Geoerg, Bettina Meissburger, Ivo Buchhalter, Marinela Augustin, Walter E. Aulitzky, Peter Hohenberger, Matthias Kroiss, Peter Schirmacher, Richard F. Schlenk, Ulrich Keilholz, Frederick Klauschen, Gunnar Folprecht, Sebastian Bauer, Jens Thomas Siveke, Christian H. Brandts, Thomas Kindler, Melanie Boerries, Anna L. Illert, Nikolas von Bubnoff, Philipp J. Jost, Karsten Spiekermann, Michael Bitzer, Klaus Schulze-Osthoff, Christof von Kalle, Barbara Klink, Benedikt Brors, Albrecht Stenzinger, Evelin Schroeck, Daniel Huebschmann, Wilko Weichert, Hanno Glimm, Stefan Froehling
Summary: Comprehensive molecular analysis in rare cancers can lead to evidence-based management recommendations and significantly improved clinical outcomes, paving the way for future clinical trials and potentially improving access to experimental treatments for this underserved patient population.
Article
Oncology
Michael Bitzer, Stephan Spahn, Sepideh Babaei, Marius Horger, Stephan Singer, Klaus Schulze-Osthoff, Pavlos Missios, Sergios Gatidis, Dominik Nann, Sven Mattern, Veit Scheble, Konstantin Nikolaou, Sorin Armeanu-Ebinger, Martin Schulze, Christopher Schroeder, Saskia Biskup, Janina Beha, Manfred Claassen, Kristina Ruhm, Antti Poso, Nisar P. Malek
Summary: In this study, two iCCA patients with extracellular and juxtamembrane FGFR2 mutations were treated with an FGFR-inhibiting tyrosine kinase inhibitor under the guidance of MTB, leading to rapid and prolonged partial response. This suggests the importance of predicting the functional consequences of FGFR2 mutations for guiding treatment decisions in iCCA patients.
NPJ PRECISION ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Beatriz Gomez Solsona, Anja Schmitt, Klaus Schulze-Osthoff, Stephan Hailfinger
Summary: The paracaspase MALT1 plays a crucial role in immune system and its deregulated activity is associated with cancer. Pharmacological targeting of MALT1 may represent a promising anti-cancer strategy.
Article
Medicine, General & Internal
Katharina John, Martin Franck, Sherin Al Aoua, Monika Rau, Yvonne Huber, Joern M. Schattenberg, Andreas Geier, Matthias J. Bahr, Heiner Wedemeyer, Klaus Schulze-Osthoff, Heike Bantel
Summary: The combination of FIB-4 and M30 allows for a more reliable identification of patients at risk for progressed NAFLD and has the potential to improve patient stratification.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Oncology
Christoph E. Heilig, Andreas Lassmann, Sadaf S. Mughal, Andreas Mock, Sebastian Pirmann, Veronica Teleanu, Marcus Renner, Carolin Andresen, Bruno C. Kohler, Bogac Aybey, Sebastian Bauer, Jens T. Siveke, Rainer Hamacher, Gunnar Folprecht, Stephan Richter, Evelin Schrock, Christian H. Brandts, Marit Ahrens, Peter Hohenberger, Gerlinde Egerer, Thomas Kindler, Melanie Boerries, Anna L. Illert, Nikolas von Bubnoff, Leonidas Apostolidis, Philipp J. Jost, C. Benedikt Westphalen, Wilko Weichert, Ulrich Keilholz, Frederick Klauschen, Katja Beck, Ulrike Winter, Daniela Richter, Lino Mohrmann, Michael Bitzer, Klaus Schulze-Osthoff, Benedikt Brors, Gunhild Mechtersheimer, Simon Kreutzfeldt, Christoph Heining, Daniel B. Lipka, Albrecht Stenzinger, Richard F. Schlenk, Peter Horak, Hanno Glimm, Daniel Hubschmann, Stefan Frohling
Summary: The expression levels of NTRK3, IGF1R, and KDR genes are associated with progression-free survival in patients with sarcoma treated with pazopanib. A pazopanib efficacy predictor can be developed based on the expression levels of these genes to accurately predict treatment outcomes for patients.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Gastroenterology & Hepatology
Paula Hoffmeister-Wittmann, Andreas Mock, Federico Nichetti, Felix Korell, Christop E. Heilig, Anna-Lena Scherr, Michael Gunther, Thomas Albrecht, Eblina Kelmendi, Kaiyu Xu, Luisa Nader, Annika Kessler, Nathalie Schmitt, Sarah Fritzsche, Sofia Weiler, Benjamin Sobol, Albrecht Stenzinger, Stefan Boeck, Christoph B. Westphalen, Klaus Schulze-Osthoff, Jorg Trojan, Thomas Kindler, Wilko Weichert, Karsten Spiekermann, Michael Bitzer, Gunnar Folprecht, Anna-Lena Illert, Melanie Boerries, Frederick Klauschen, Sebastian Ochsenreiter, Jens Siveke, Sebastian Bauer, Hanno Glimm, Benedikt Brors, Jennifer Huellein, Daniel Huebschmann, Sebastian Uhrig, Peter Horak, Simon Kreutzfeld, Jesus M. Banales, Christoph Springfeld, Dirk Jaeger, Peter Schirmacher, Stephanie Roessler, Steffen Ormanns, Benjamin Goeppert, Stefan Froehling, Bruno C. Koehler
Summary: The study identified Bcl-x(L) as a key protein in cell death resistance of CCA and suggested its potential prognostic value, serving as a potential therapeutic target.
LIVER INTERNATIONAL
(2022)
Article
Dermatology
Sofie Kaas Ovesen, Klaus Schulze-Osthoff, Lars Iversen, Claus Johansen
Summary: This study reveals a novel crucial regulatory mechanism by which TNF alpha and IL-17A cooperate to regulate the expression of IL-36 gamma in psoriasis, involving the key regulator NFKBIZ and signaling pathways including NF-kappa B, p38 mitogen-activated protein kinase, and ERK1/2.
ACTA DERMATO-VENEREOLOGICA
(2021)
