Review
Cell Biology
Lawrence M. Schwartz
Summary: Cell death is a normal and essential component of development and homeostasis, but dysregulation of this process underlies most human diseases. Autophagy is a process mediated by the formation of double membrane vesicles, which allows cells to survive stresses and may also mediate cell death during development and pathogenesis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Dentistry, Oral Surgery & Medicine
Xu Wang, Weiwei Zhao, Wenqing Zhang, Shuangshuang Wu, Zhimin Yan
Summary: This study reveals that C. albicans infection could induce upregulation of PD-L1 in OSCC, which can be observed in vitro and in a mouse model. The activation of TLR2/MyD88 and TLR2/NF-κB pathways may contribute to the regulation of PD-L1 expression induced by C. albicans infection.
JOURNAL OF ORAL PATHOLOGY & MEDICINE
(2022)
Article
Plant Sciences
Huong Giang Le, Jung-Mi Kang, Tuan Cuong Vo, Byoung-Kuk Na
Summary: The study found that kaempferol has anti-amoebic effects against Naegleria fowleri and can induce programmed cell death through apoptosis-like pathway and autophagy pathway. This research is of great significance for the development and optimization of therapeutic drugs for primary amoebic meningoencephalitis (PAM).
Article
Toxicology
Li Zhang, Shichen Xu, Xian Cheng, Jing Wu, Liying Wu, Yunping Wang, Xiaowen Wang, Jiandong Bao, Huixin Yu
Summary: Curcumin significantly inhibits the growth of thyroid cancer cells by inducing autophagy through activation of the MAPK pathway and inhibition of the mTOR pathway. It exerts selective cytotoxicity on thyroid cancer cells without affecting normal epithelial cells, suggesting that inducing autophagic cell death may serve as a potential anti-cancer strategy for thyroid cancer.
TOXICOLOGY IN VITRO
(2022)
Article
Environmental Sciences
Fang Bai, Yunlu Jia, Jie Li, Zhongxing Wu, Lin Li, Lirong Song
Summary: This study found that programmed cell death (PCD) in cyanobacterium Microcystis aeruginosa and green algae Chlorella luteoviridis induced by paraquat involved the caspase-dependent pathway. However, the signaling pathway and cascade events of PCD differed between the two species. In M. aeruginosa, cell death was triggered by a rapid increase in free Ca2+ concentration followed by elevated reactive oxygen species (ROS) levels, while in C. luteoviridis, cell death was mediated by the mitochondrial apoptosis pathway along with increased ROS levels and caspase-like activity. Furthermore, the levels of ROS and metacaspase activity were synchronized in both species, implying that paraquat-induced PCD was ROS-mediated.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Chemistry, Multidisciplinary
Chang-feng Song, Yu-heng Hu, Zhi-guo Mang, Zeng Ye, Hai-di Chen, De-sheng Jing, Gui-xiong Fan, Shun-rong Ji, Xian-jun Yu, Xiao-wu Xu, Yi Qin
Summary: In this study, the researchers investigated the role of autophagy in Her-induced cell death in human pancreatic cancer cell lines. They found that Her dose-dependently suppressed cell proliferation, promoted autophagy, and induced autophagic death in pancreatic ductal adenocarcinoma (PDAC) cell lines. Moreover, Her activated autophagy by increasing the phosphorylation of AMPK and decreasing the phosphorylation of mTOR/p70S6K. The study provides evidence for the development of Her as a therapeutic agent for the treatment of pancreatic cancer.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Oncology
Tianqi Liu, Chen Zhu, Xin Chen, Gefei Guan, Cunyi Zou, Shuai Shen, Jianqi Wu, Yuhang Wang, Zhiguo Lin, Ling Chen, Peng Cheng, Wen Cheng, Anhua Wu
Summary: This study reveals the importance of ferroptosis in glioma and proposes a novel immunotherapeutic strategy that combines immune checkpoint blockade treatment with ferroptosis inhibition, showing a synergistic therapeutic effect.
Article
Multidisciplinary Sciences
Soumi Sadhu, Sanjay Kumar, Dipendra Kumar Mitra, Beenu Joshi
Summary: Pathogen detection is the most important stage in activating an appropriate immune response during an infection. In leprosy patients, the expression patterns of TLR2 and TLR4 are associated with the immunosuppressive markers PD-1 and PD-L1, and blocking the interaction of PD-1 and PD-L1 can improve immune activation status.
Article
Immunology
Baoshan Wang, Dazhou Li, Dehua Zeng, Wen Wang, Chuanshen Jiang
Summary: We report a rare case of a middle-aged woman with progressive upper abdominal pain and melena. Laboratory testing showed elevated level of carcinoembryonic antigen. Imaging and cytologic studies excluded metastasis and confirmed primary periampullary squamous cell carcinoma. The tumor had high expression of programmed cell death-ligand 1 (PD-L1), and the patient responded well to chemotherapy combined with immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Heming Li, Zhi Wang, Shanshan Liang, Qiuge Liu, Piao Wang, Longyu Cai, Ruoyu Wang
Summary: This study revealed that long-term radiation induces epithelial-mesenchymal transition and increases migration ability of nasopharyngeal carcinoma radioresistant cells through upregulation of programmed cell death ligand-1 (PD-L1), suggesting potential interventions to reverse EMT-induced acquisition of radioresistance.
TRANSLATIONAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Min-Hee Jo, Yong-Tae Kim, Sun Joo Park
Summary: Dieckol, a natural polyphenol, inhibits the growth of melanoma cells by inducing apoptotic cell death through affecting lysosomal function and mitochondrial membrane. This suggests its potential value as a chemotherapeutic drug candidate for melanoma treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Meng Li, Ping Zhang, Wenping Xu, Jianzhong Yuan, Qingfeng Li, Liming Tao, Zhong Li, Yang Zhang
Summary: This study evaluated the cytotoxicity and mode of action of Avermectin (AVM) in Spodoptera frugiperda (Sf9) cells, showing that AVM induced DNA damage and programmed cell death in Sf9 cells. The results suggest that AVM may induce autophagy through the AMPK/mTOR-mediated pathway.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2021)
Article
Agriculture, Dairy & Animal Science
Takuo Hojo, Dariusz J. Skarzynski, Kiyoshi Okuda
Summary: This article presents recent findings on the mechanisms of programmed cell death (PCD) in the regression of the corpus luteum (CL) in mammals. It focuses on apoptosis, autophagic cell death (ACD), and necroptosis as the three main types of PCD that contribute to bovine CL regression.
JOURNAL OF REPRODUCTION AND DEVELOPMENT
(2022)
Article
Oncology
Xinyi Zhou, Dongliang Fu, Hang Yang, Chenqin Le, Yier Lu, Jingsun Wei, Yang Tang, Jiawei Zhang, Ying Yuan, Kefeng Ding, Qian Xiao
Summary: In our experiments, we observed that Rigosertib (RGS) exhibited tumor growth arrest and robust anti-tumor immunity in colorectal cancer (CRC) isograft tumors in immunocompetent mice. RGS down-regulated programmed cell death ligand 1 (PD-L1) expression and induced autophagy in CRC cells. Additionally, RGS showed synergistic anti-tumor activity with cytotoxic T-lymphocyte-associated protein 4 monoclonal antibody. Overall, RGS could be a promising drug for CRC therapy.
Review
Cell Biology
Elizabeth G. Ames, Jess G. Thoene
Summary: Cystinosis is a lethal genetic disease with specific treatments. The cellular mechanisms are still unknown, but programmed cell death and apoptosis may be involved. Studies have shown that apoptosis rate is increased in cystinosis, but can be partially reversed with cysteamine.
Editorial Material
Gastroenterology & Hepatology
Nadine Martin, Dorian V. Ziegler, Romain Parent, David Bernard
Article
Biochemistry & Molecular Biology
Delphine Fessart, Claire de Barbeyrac, Ines Boutin, Thomas Grenier, Elodie Richard, Hughes Begueret, David Bernard, Eric Chevet, Jacques Robert, Frederic Delom
Summary: AGR2 acts as a growth factor in the tumor microenvironment by enhancing tumor cell growth through repression of p21(CIP1). Targeting the eAGR2/p21(CIP1) signaling pathway may be a potential therapeutic strategy to inhibit tumor growth.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Letter
Biochemistry & Molecular Biology
Larissa Lipskaia, Pauline Maisonnasse, Charles Fouillade, Valentin Sencio, Quentin Pascal, Jean-Michel Flaman, Emmanuelle Born, Arturo London-Vallejo, Roger Le Grand, David Bernard, Francois Trottein, Serge Adnot
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Valerio Farfariello, Dmitri Gordienko, Lina Mesilmany, Yasmine Touil, Emmanuelle Germain, Ingrid Fliniaux, Emilie Desruelles, Dimitra Gkika, Morad Roudbaraki, George Shapovalov, Lucile Noyer, Mathilde Lebas, Laurent Allart, Nathalie Zienthal-Gelus, Oksana Iamshanova, Franck Bonardi, Martin Figeac, William Laine, Jerome Kluza, Philippe Marchetti, Bruno Quesnel, Daniel Metzger, David Bernard, Jan B. Parys, Loic Lemonnier, Natalia Prevarskaya
Summary: This study reveals the mechanism of how alterations in mitochondrial function and calcium signaling contribute to cellular senescence and tumor growth. The downregulation of TRPC3 protein in senescent fibroblasts leads to increased mitochondrial calcium load and oxidative phosphorylation, promoting cellular senescence. The downregulation of TRPC3 in stromal cells also affects secretome and tumor progression, highlighting its importance in cancer development.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Clotilde Raynard, Xingjie Ma, Anda Huna, Nolwenn Tessier, Amelie Massemin, Kexin Zhu, Jean-Michel Flaman, Florentin Moulin, Delphine Goehrig, Jean-Jacques Medard, David Vindrieux, Isabelle Treilleux, Hector Hernandez-Vargas, Sylvie Ducreux, Nadine Martin, David Bernard
Summary: Cellular senescence is characterized by stable proliferation arrest and the acquisition of a senescence-associated secretory phenotype (SASP). The SASP affects the environment of senescent cells and can induce different phenotypic changes. This study reveals that the SASP can promote the neuroendocrine transdifferentiation (NED) of some epithelial cancer cells, providing insights into the functional link between senescent cell accumulation, NED, and clinical patient outcome.
Article
Biochemistry & Molecular Biology
Aaron Mendez-Bermudez, Liudmyla Lototska, Melanie Pousse, Florent Tessier, Oliver Croce, Chrysa M. Latrick, Veronica Cherdyntseva, Joe Nassour, Jiang Xiaohua, Yiming Lu, Corinne Abbadie, Sarantis Gagos, Jing Ye, Eric Gilson
Summary: Cellular senescence triggers various types of heterochromatin remodeling, including decondensation, DNA damage, and illegitimate recombination. In this study, it was discovered that at the onset of senescence, pericentromeric heterochromatin is specifically dismantled due to telomere shortening or genotoxic stress. This process is initiated by the TP53-TRF2 axis and involves the downregulation of TRF2, resulting in heterochromatin decondensation and DNA breaks.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Oncology
Alberta Palazzo, Hector Hernandez-Vargas, Delphine Goehrig, Jean-Jacques Medard, David Vindrieux, Jean-Michel Flaman, David Bernard
Summary: Cancer cells arising from senescent cells display more aggressive features and resistance to drugs. A molecular signature of these cells can serve as a prognostic marker for several human cancers.
Article
Biochemistry & Molecular Biology
Clotilde Raynard, Nolwenn Tessier, Anda Huna, Marine Warnier, Jean-Michel Flaman, Fabien Van Coppenolle, Sylvie Ducreux, Nadine Martin, David Bernard
Summary: The regulation of calcium ion (Ca2+) levels during cellular senescence is not well understood. This study found that several senescence inducers increased intracellular Ca2+ content in human mammary epithelial cells (HMECs), and the expression of the Ca2+-binding protein CALB1 was upregulated through the Ca2+-dependent calcineurin/NFAT pathway. Overexpression of CALB1 buffered the rise in intracellular Ca2+ levels observed in senescent cells. Additionally, increased expression of Ca2+-binding proteins calbindins was found to be a common marker of senescent cells. These findings suggest that Ca2+ and Ca2+-binding proteins play a crucial role in regulating cellular senescence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Emmanuelle Born, Larissa Lipskaia, Marielle Breau, Amal Houssaini, Delphine Beaulieu, Elisabeth Marcos, Remi Pierre, Marcio Do Cruzeiro, Marine Lefevre, Genevieve Derumeaux, Dmitry V. Bulavin, Marion Delcroix, Rozenn Quarck, Virinder Reen, Jesus Gil, David Bernard, Jean-Michel Flaman, Serge Adnot, Shariq Abid
Summary: This study investigated the role of senescent cells in patients with pulmonary arterial hypertension and animal models. The findings revealed that clearance of senescent cells resulted in vascular remodeling and damage to the pulmonary artery.
Review
Cell Biology
Nadine Martin, Kexin Zhu, Joanna Czarnecka-Herok, Mathieu Vernier, David Bernard
Summary: Cellular senescence is a state of cell proliferation arrest accompanied by a specific secretory program, which affects the microenvironment of senescent cells. Various stresses can induce cellular senescence, such as telomere shortening, oncogene activation, oxidative or genotoxic stress. Cellular senescence plays a crucial role throughout life, showing beneficial effects in embryonic development and wound healing, but also detrimental effects in aging and aging-related diseases. In recent years, calcium and calcium signaling have been identified as critical factors in the implementation and regulation of cellular senescence. This review highlights the main discoveries in this field, including the increased intracellular calcium concentration in senescent cells, the identification of calcium-binding proteins, calcium channels (TRP, ITPR, ...), and MERCs (mitochondria-endoplasmic reticulum contact sites) as key players in this context.
Review
Cell Biology
Nadine Martin, Nikolay Popgeorgiev, Gabriel Ichim, David Bernard
Summary: In this Comment, the authors highlight the non-apoptotic roles of BCL-2 proteins in regulating cellular senescence and caution against the use of BCL-2 inhibitors as senolytics. While BCL-2 and related proteins are known for their role in apoptosis regulation, recent findings suggest their involvement in cellular senescence through non-apoptotic mechanisms.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sara Jaber, Marine Warnier, Christopher Leers, Mathieu Vernier, Delphine Goehrig, Jean-Jacques Medard, David Vindrieux, Dorian V. V. Ziegler, David Bernard
Summary: This study found that pancreatic cancer cells have strong resistance to available treatments, but a drug can induce these cells into a senescent-like state, and can kill them by targeting specific proteins. This provides a potential strategy to improve the efficacy of conventional chemotherapies against pancreatic cancer.
MOLECULAR BIOMEDICINE
(2023)
Article
Cell Biology
Lou Delval, Aline Hantute-Ghesquier, Valentin Sencio, Jean Michel Flaman, Cyril Robil, Fabiola Silva Angulo, Larissa Lipskaia, Ozmen cobanoglu, Anne-Sophie Lacoste, Arnaud Machelart, Adeline Danneels, Mathieu Corbin, Lucie Deruyter, Severine Heumel, Thierry Idziorek, Karin Seron, Florent Sauve, Antonino Bongiovanni, Vincent Prevot, Isabelle Wolowczuk, Sandrine Belouzard, Jean-Michel Saliou, Philippe Gosset, David Bernard, Yves Rouille, Serge Adnot, Martine Duterque-Coquillaud, Francois Trottein
Summary: This study found that age-associated cellular senescence is a factor contributing to the severity of COVID-19. Aged hamsters accumulate senescent cells in the lungs, and ABT-263 can deplete these cells. Compared to young hamsters, aged hamsters have a higher viral load and more complications during COVID-19. Early treatment with ABT-263 can reduce pulmonary viral load and improve lung disease.
Article
Oncology
Anda Huna, Jean-Michel Flaman, Catalina Lodillinsky, Kexin Zhu, Gabriela Makulyte, Victoria Pakulska, Yohann Coute, Clemence Ruisseaux, Pierre Saintigny, Hector Hernandez-Vargas, Pierre-Antoine Defossez, Mathieu Boissan, Nadine Martin, David Bernard
Summary: The study revealed that RSK3 can promote escape from TGF beta-induced senescence by inhibiting the NF-kappa Beta pathway, shifting the cell fate from senescence to malignancy. This finding provides a novel insight into the understanding of cell fate switching in TGF beta signaling, which may be relevant to tumor progression.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Ozmen Cobanoglu, Lou Delval, Daniele Ferrari, Lucie Deruyter, Severine Heumel, Isabelle Wolowczuk, Abir Hussein, Ayse Nur Menevse, David Bernard, Philip Beckhove, Frauke Alves, Francois Trottein
Summary: The decline in immunity due to aging reduces the effectiveness of vaccines in older adults. Removing senescent cells before vaccination can modify immune responses, but caution should be taken as it may reduce vaccine protection against certain diseases in older individuals.