Article
Oncology
Khalid Rashid, Christian Roeder, Freya Goumas, Jan-Hendrik Egberts, Holger Kalthoff
Summary: In this study, the inhibition of CD95 signaling altered the chemotherapeutic effects of gemcitabine by suppressing the pro-inflammatory responses from CD95L-positive tumor cells as well as from the TNF-a and TRAIL signaling in a bi-lateral crosstalk manner.
Review
Physiology
Laurel A. Grisanti
Summary: Cardiovascular disease is a leading cause of death globally. Cardiomyocyte death, which occurs in heart damage and stress, contributes to cardiac dysfunction and further damages the heart. Apoptosis, a regulated form of cell death, can occur through intrinsic or extrinsic pathways. The poorly characterized TNF-related ligand TRAIL and its receptors have been found to play a role in cardiac pathology. This article aims to provide an overview of the current understanding of TRAIL and its receptors in normal and pathological conditions in the heart.
FRONTIERS IN PHYSIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Longfei Deng, Xuan Zhai, Ping Liang, Hongjuan Cui
Summary: TRAIL holds therapeutic potential in cancer treatment, but many cancers, including GBM, exhibit resistance. Recent studies have identified new mechanisms in regulating TRAIL-induced apoptosis in GBM and effective combinatorial strategies. The TRAIL/TRAIL death receptor axis may have future clinical applications for GBM treatment.
Review
Biochemistry & Molecular Biology
You-Take Oh, Shi-Yong Sun
Summary: The involvement of the TRAIL/death receptor signaling pathway in the regulation of cancer invasion and metastasis is complex, with both positive and negative roles reported. The underlying molecular mechanisms are even more complicated. This review focuses on discussing the current understanding of how TRAIL/death receptor-mediated signaling regulates cancer cell invasion and metastasis.
Review
Immunology
Yanrui Zhang, Taian Jin, Zhangqi Dou, Boxing Wei, Buyi Zhang, Chongran Sun
Summary: The binding of CD95 to CD95L triggers a cascade of signals leading to apoptosis, but most tumor cells are resistant to CD95L-induced apoptosis. In some cancers, the CD95-CD95L binding promotes tumor growth. This review summarizes the potential mechanisms of non-apoptotic signaling and the expression of CD95L in other cell types.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Eden Lebrault, Christelle Oblet, Keerthi Kurma, Nicolas Levoin, Robin Jeannet, Mickael Jean, Pierre Vacher, Patrick Legembre
Summary: This study investigates the stoichiometry of CD95L required for apoptotic and nonapoptotic signals. The researchers generated CD95L concatemers of different chemistries and found that a hexameric structure is best for triggering cell death, while a dimer is sufficient for inducing apoptotic response in CD95-sensitive cells. Interestingly, trimeric and hexameric forms are the only ones capable of implementing a potent Ca2+ response, indicating the requirement for both aggregation and conformation to activate the Ca2+ pathway.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Layla Haymour, Mickael Jean, Cristian Smulski, Patrick Legembre
Summary: The interaction between CD95L and CD95 plays a crucial role in maintaining tissue homeostasis and eliminating infected and cancer cells. However, this interaction can also activate non-apoptotic signaling pathways that contribute to cancer metastasis and auto-immune disorders. Moreover, CD95 expression itself may promote oncogenesis independently of CD95L, and both ligand and receptor can interact with other partners to modulate their physiological functions. Therefore, understanding these non-canonical responses is essential for elucidating the functions of the CD95L-CD95 pair.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Article
Environmental Sciences
Haojie Li, Junjiang Fan, Yangfei Zhao, Jiarong Yang, Huimiao Xu, Ram Kumar Manthari, Xiaofang Cheng, Jundong Wang, Jinming Wang
Summary: The study shows that long-term excessive intake of fluoride can cause kidney damage and apoptosis, while dietary calcium supplementation can alleviate this damage. Calcium supplementation mitigates fluoride-induced kidney apoptosis through various signaling pathways.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Biochemistry & Molecular Biology
Liya Qin, Jian Zou, Alexandra Barnett, Ryan P. Vetreno, Fulton T. Crews, Leon G. Coleman
Summary: The study reports the role of TLR7-mediated apoptotic neuronal death in alcohol use disorder. It suggests that TRAIL may act as a mediator of neuronal apoptosis downstream of TLR7 activation and represent a potential therapeutic target for slowing neurodegeneration in multiple diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
K. M. A. Zinnah, Sang-Youel Park
Summary: The study demonstrated the mechanism behind the synergistic anticancer effect of amitriptyline and TRAIL, showing that amitriptyline increases TRAIL-induced apoptosis by upregulating death receptors DR4 and DR5. Inhibition of autophagy by amitriptyline was also shown to enhance DR4 and DR5 expression.
Article
Physiology
Javier Fernandez-Diaz, Roberto Beteta-Goebel, Manuel Torres, Joan Cabot, Paula Fernandez-Garcia, Victoria Llado, Pablo V. Escriba, Xavier Busquets
Summary: This study investigated the activity of a synthetic lipid, TGM4, on pancreatic cancer cells and found that it inhibited cell proliferation and induced cell death through the activation of cytocidal autophagy. These findings highlight the importance of lipid signaling in cancer and suggest synthetic lipid structures as potential approaches to treat pancreatic cancer and other neoplasias.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Genetics & Heredity
Atsushi Watanabe, Kunio Miyake, Koshi Akahane, Kumiko Goi, Keiko Kagami, Hideo Yagita, Takeshi Inukai
Summary: Immunotherapies specific for BCP-ALL, such as anti-CD19 CAR T-cells and blinatumomab, have significantly improved outcomes in refractory cases. The methylation status of DR4 and DR5 genes is associated with gene expression levels, cell-surface expression, and TRAIL-sensitivities, suggesting potential clinical relevance in predicting immunotherapy efficacy. Evaluating methylation status of DR4 and DR5 genes may be informative in certain cases with unfavorable karyotypes.
Review
Cell Biology
Vesna Risso, Elodie Lafont, Matthieu Le Gallo
Summary: Cell death is crucial for tissue homeostasis. The CD95/CD95L pathway is involved in various diseases, including cancer, autoimmune diseases, and chronic inflammation. Apart from inducing apoptosis, CD95L also triggers non-apoptotic signaling, contributing to tumor-promoting and pro-inflammatory roles. Understanding the role of CD95/CD95L in these diseases may guide the development of therapeutic strategies.
CELL DEATH & DISEASE
(2022)
Article
Pharmacology & Pharmacy
Guojun Zhang, Mingkai Xu, Xiaoqing Zhang, Ling Ma, Huiwen Zhang
Summary: SAM-1 can activate T cells and induce apoptosis in human tumor cells by regulating dendritic cell signaling pathways and cytokine production, mediated through TRAIL.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Article
Cell Biology
Emir Bozkurt, Heiko Dussmann, Manuela Salvucci, Brenton L. Cavanagh, Sandra Van Schaeybroeck, Daniel B. Longley, Seamus J. Martin, Jochen H. M. Prehn
Summary: The study reveals that TRAIL signaling not only activates apoptosis in colon cancer cells but also induces entosis through TRAIL receptors and the structural presence of caspase-8. The association of TRAIL signaling with cell-in-cell structures is significant in colorectal cancer, especially in the context of patient prognosis. Factors controlling entosis in tumors remain to be elucidated despite the evidence of entosis in cancers.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Immunology
Doaa Tawfik, Christopher Groth, Jan-Paul Gundlach, Matthias Peipp, Dieter Kabelitz, Thomas Becker, Hans-Heinrich Oberg, Anna Trauzold, Daniela Wesch
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Oncology
Ufuk Mert, Alshaimaa Adawy, Elisabeth Scharff, Pierre Teichmann, Anna Willms, Verena Haselmann, Cynthia Colmorgen, Johannes Lemke, Silvia von Karstedt, Juergen Fritsch, Anna Trauzold
Article
Obstetrics & Gynecology
Thorsten Heilmann, Anna-Lena Rumpf, Marijke Roscher, Maren Tietgen, Olga Will, Mirko Gerle, Timo Damm, Christoph Borzikowsky, Nicolai Maass, Claus-Christian Glueer, Sanjay Tiwari, Anna Trauzold, Christian Schem
ARCHIVES OF GYNECOLOGY AND OBSTETRICS
(2020)
Article
Oncology
Doaa Tawfik, Angela Zaccagnino, Alexander Bernt, Monika Szczepanowski, Wolfram Klapper, Albrecht Schwab, Holger Kalthoff, Anna Trauzold
Article
Medicine, General & Internal
Florian Richter, Annette Baratay, Christian Roeder, Jan-Hendrik Egberts, Holger Kalthoff, Thomas Becker, Susanne Sebens
JOURNAL OF CLINICAL MEDICINE
(2020)
Article
Gastroenterology & Hepatology
Bastian Kettler, Anna Trauzold, Christian Roeder, Jan-Hendrik Egberts, Holger Kalthoff
Summary: In this study, subcutaneous and orthotopic inoculation of Colo357 Bcl-x(L) cell-derived tumors were compared with and without TRAIL treatment. The results showed that orthotopically inoculated tumors were smaller but exhibited more liver metastasis than subcutaneously inoculated tumors. This highlights the importance of the proper inoculation site for PDAC cells.
HEPATOBILIARY & PANCREATIC DISEASES INTERNATIONAL
(2021)
Article
Oncology
Jan-Paul Gundlach, Charlotte Hauser, Franka Maria Schlegel, Anna Willms, Christine Halske, Christian Roder, Sandra Kruger, Christoph Rocken, Thomas Becker, Holger Kalthoff, Anna Trauzold
Summary: HMGA2 expression in the nucleus is associated with tumor dedifferentiation and lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC). The presence of HMGA2 in both the cytoplasm and the nucleus of tumor cells is common, with stronger nuclear staining observed. Additionally, cytoplasmic HMGA2 expression correlates with lymph vessel and venous invasion, suggesting a potential role in nodal spread.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Cell Biology
Anna Willms, Hella Schupp, Michelle Poelker, Alshaimaa Adawy, Jan Frederik Debus, Torsten Hartwig, Tim Krichel, Juergen Fritsch, Steven Singh, Henning Walczak, Silvia von Karstedt, Heiner Schaefer, Anna Trauzold
Summary: TRAIL-R2 can induce apoptosis in cancer cells but also have pro-tumor functions, interacting with p53 in the nucleus to regulate its levels and affect the expression of p53 target genes.
CELL DEATH & DISEASE
(2021)
Article
Medicine, General & Internal
Dorothee Winterberg, Lennart Lenk, Maren Osswald, Fotini Vogiatzi, Carina Lynn Gehlert, Fabian-Simon Frielitz, Katja Klausz, Thies Roesner, Thomas Valerius, Anna Trauzold, Matthias Peipp, Christian Kellner, Denis Martin Schewe
Summary: BCP-ALL is a common malignancy in children with high cure rates but toxic chemotherapy. A novel CD19-TRAIL antibody showed efficient killing of BCP-ALL cells and prolonged survival of mice, suggesting its potential as an immunotherapeutic agent against BCP-ALL.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, General & Internal
Jan-Paul Gundlach, Jannik Kerber, Alexander Hendricks, Alexander Bernsmeier, Christine Halske, Christian Roeder, Thomas Becker, Christoph Roecken, Felix Braun, Susanne Sebens, Nils Heits
Summary: This study reveals that cancer-associated fibroblasts (CAF) and Schwann cells (SC) have differential impact on cholangiocarcinoma (CCA) cells. The multityrosine kinase-inhibitor Sorafenib partially reverses these stroma-mediated effects. These findings contribute to a better understanding of the paracrine interplay of CAF and SC with CCA cells.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Cell Biology
Sofie Hagelund, Anna Trauzold
Summary: TRAIL plays a crucial role in tumor immune surveillance and has the potential to kill cancer cells, but faces challenges in clinical trials. The external pH influences PDAC cells' response to TRAIL, with acidic pH adaptation showing the ability to enhance TRAIL sensitivity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Anna-Christina Rambow, Insa Aschenbach, Sofie Hagelund, Doaa Tawfik, Jan-Paul Gundlach, Sebastian Weisse, Nicolai Maass, Anna Trauzold
Summary: Binding of TRAIL to its death domain-containing receptors TRAIL-R1 and TRAIL-R2 can induce cell death and/or pro-inflammatory signaling. The importance of TRAIL and TRAIL-R1/R2 in tumor immune surveillance and cancer biology has meanwhile been well documented. TRAIL also binds to TRAIL-R3 and TRAIL-R4, which have regulatory functions in apoptotic and non-apoptotic signaling pathways. Knockdown of TRAIL-R4 affects the activation of apoptotic and non-apoptotic pathways in cancer cells, showing opposing effects on cell death and clonogenic survival. TRAIL-R4 also regulates the expression of anti-apoptotic proteins and affects the activity of AKT, ERK, p38 and NF-kappa B. This study provides evidence for the important role of endogenous TRAIL-R4 in cancer cells and improves the understanding of the complex TRAIL/TRAIL-R system in humans.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Physiology
Christiane E. Sorensen, Anna Trauzold, Nynne M. Christensen, Doaa Tawfik, Monika Szczepanowski, Ivana Novak
Summary: The mechanisms of synergistic agonist stimulation and modulation of anion secretion in human pancreatic duct epithelial cells are still not fully understood. This study aims to explore these mechanisms in the Capan-1 monolayer model and found that combined agonist stimulation enhances anion transport responses. The inhibition of H+,K+-ATPase also affects anion transport in Capan-1 monolayers. Furthermore, the expression and function of K+ channels in Capan-1 were analyzed, revealing their potential role in anion secretion and pH and potassium homeostasis.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nourhane Ammar, Maya Hildebrandt, Claudia Geismann, Christian Roeder, Timo Gemoll, Susanne Sebens, Ania Trauzold, Heiner Schaefer
Summary: Pancreatic ductal adenocarcinoma (PDAC) cells adapt their metabolism to glutamine scarcity and develop resistance against anticancer treatments through the reverse Warburg phenotype and MCT1-mediated lactate uptake.
Article
Biotechnology & Applied Microbiology
Thorsten Heilmann, Florian Vondung, Christoph Borzikowsky, Sandra Krueger, Mohamed Elessawy, Ibrahim Alkatout, Antonia Wenners, Maret Bauer, Wolfram Klapper, Christoph Roecken, Nicolai Maass, Christian Schem, Anna Trauzold
INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS
(2020)
Article
Cell Biology
Mohamed Kodiha, Nabila Azad, Siwei Chu, Noah Crampton, Ursula Stochaj
Summary: This study reveals that oxidative stress induces the nuclear accumulation of RanBP1 and the signaling pathways mediated by EGFR and PKA play a role in regulating RanBP1 localization during stress. RanBP1 acts as a downstream effector of these signaling routes, positioning it at the intersection of important cellular signaling circuits.
EUROPEAN JOURNAL OF CELL BIOLOGY
(2024)