Article
Cell Biology
Yaxuan Wang, Haixia Zhu, Haifei Xu, Yifan Qiu, Yonghong Zhu, Xiaolin Wang
Summary: Patients with advanced bladder cancer often develop chemoresistance, leading to tumor recurrence. In this study, the senescence program in solid tumors was shown to improve short-term drug sensitivity. The important role of c-Myc in bladder cancer cell senescence was determined using bioinformatics analysis. The study also revealed that reducing the expression levels of c-Myc and HSP90B1 could inhibit bladder cancer cell proliferation, promote cellular senescence, and enhance cisplatin chemosensitivity. The HSP90B1/c-Myc interaction was found to regulate the p21 signaling pathway, which affects cisplatin sensitivity by modulating bladder cancer cell senescence.
Article
Chemistry, Medicinal
Qing Huang, Chunlan Pu, Lun Tan, Shirui Wang, Hongjia Zhang, Su Yu, Rui Deng, Dan Luo, Xinyu Ma, Rui Li
Summary: c-Myc protein, aberrantly expressed in colorectal cancer, can be effectively inhibited by a compound called B13. B13 not only suppresses the proliferation and migration of CRC cells, but also interferes with the expression of apoptosis pathway-related proteins. Additionally, B13 shows strong inhibition of tumor growth in animal models.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Letter
Oncology
Long Chen, Anqi Ren, Yuan Zhao, Hangyu Chen, Qifang Wu, Mengzhu Zheng, Zijian Zhang, Tongcun Zhang, Wu Zhong, Jian Lin, Haichuan Zhu
Summary: In this study, the researchers discovered that TET1, a key participant in DNA epigenetic control, is highly upregulated in T-cell acute lymphoblastic leukemia (T-ALL) and is negatively correlated with patient prognosis. Knockdown of TET1 suppressed T-ALL growth and progression, suggesting that TET1 inhibition might be an effective way to treat T-ALL. Additionally, the researchers found that auranofin, a gold-containing compound, is a potent TET1 inhibitor, which can reprogram gene expression and inhibit T-ALL growth.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Chemistry, Medicinal
Ji Eon Park, Ji Hoon Jung, Hyo-Jung Lee, Deok Yong Sim, Eunji Im, Woon Yi Park, Bum Sang Shim, Seong-Gyu Ko, Sung-Hoon Kim
Summary: The study revealed that Sanggenon G (SanG) can inhibit the viability of non-small lung cancer cells through multiple pathways, including inhibition of cyclins and apoptosis-related proteins. Additionally, SanG can induce apoptosis by activating caspase-3 and RPL5, showing potential for combination with other drugs.
PHYTOTHERAPY RESEARCH
(2021)
Article
Medicine, Research & Experimental
Enyi Gao, Xiaoya Sun, Rick Francis Thorne, Xu Dong Zhang, Jinming Li, Fengmin Shao, Jianli Ma, Mian Wu
Summary: NIPSNAP1 is identified as a mediator of c-Myc function and a negative regulator of cellular senescence in cancer cells. It promotes cancer cell proliferation by maintaining c-Myc levels and prevents senescence by modulating ROS levels.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Monika Pawlowska, Jolanta Kulesza, Ewa Augustin
Summary: Unsymmetrical bisacridines (UAs) are highly active antitumor compounds that stabilize G-quadruplex structures and affect specific gene expression, leading to apoptosis and senescence in cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Qianqian Xu, Guangzhao Pan, Zhonglan Wang, Lingling Wang, Yancheng Tang, Jinyun Dong, Jiang-Jiang Qin
Summary: In this study, it was found that Platycodin D (PD) can inhibit gastric cancer cell viability by destabilizing the c-Myc protein, leading to cell cycle arrest and subsequent apoptosis. This novel molecular mechanism proposes a potential anti-cancer therapy using PD.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Yapei Huang, Juliana E. Shin, Alexander M. Xu, Changfu Yao, Sandy Joung, Min Wu, Ruan Zhang, Bongha Shin, Joslyn Foley, Simeon B. Mahov, Matthew E. Modes, Joseph E. Ebinger, Matthew Driver, Jonathan G. Braun, Caroline A. Jefferies, Tanyalak Parimon, Chelsea Hayes, Kimia Sobhani, Akil Merchant, Sina A. Gharib, Stanley C. Jordan, Susan Cheng, Helen S. Goodridge, Peter Chen
Summary: Host factors such as age, sex, obesity, and other comorbidities can impact the effectiveness of COVID-19 vaccines. A study identified healthcare workers with unexpectedly low antibody levels after receiving the BNT162b2 vaccine. These individuals had fewer antibody-producing cells and weaker T cell responses, potentially due to premature lymphocyte aging.
Article
Oncology
Ahmed M. Elshazly, Melanie M. Sinanian, Victoria Neely, Eesha Chakraborty, Muruj A. Alshehri, Michael K. McGrath, Hisashi Harada, Patricia V. Schoenlein, David A. Gewirtz
Summary: Breast cancer is a common malignancy in women, with ER+ breast cancer accounting for 70% of cases. Current standard treatment includes the use of estrogen antagonists and CDK4/6 inhibitors, but disease recurrence and metastasis remain a challenge. This study explores the potential of BET family inhibitors to improve the response to current therapies.
Article
Oncology
Shoichiro Tange, Tomomi Hirano, Masashi Idogawa, Eishu Hirata, Issei Imoto, Takashi Tokino
Summary: Elevated expression of MYEOV gene is significantly correlated with poor prognosis in pancreatic cancer patients, and its overexpression enhances the activation of multiple oncogenic pathways, leading to the induction of pancreatic cancer cell proliferation.
Article
Biochemistry & Molecular Biology
Song-Hee Kim, Byung-Chul Kang, Daseul Seong, Won-Hyeok Lee, Jae-Hee An, Hyoung-Uk Je, Hee-Jeong Cha, Hyo-Won Chang, Sang-Yoon Kim, Seong-Who Kim, Myung-Woul Han
Summary: This study revealed that EPHA3 regulates DNA methylation and histone methylation of PTEN through the PTEN/Akt/EMT pathway, affecting PTEN levels in radioresistant head and neck cancer cells. This provides a novel mechanism for radiotherapy resistance in these cancer cells.
Article
Cell Biology
Yanchen Wang, Pengchao Hu, Fenfen Wang, Shaoyan Xi, Shasha Wu, Liangzhan Sun, Yuyang Du, Jingyi Zheng, Hui Yang, Mao Tang, Han Gao, Hao Luo, Yue Lv, Jingsong Yan, Xijun Ou, Yan Li
Summary: The research reveals the crucial role of UHRF1 in regulating liver cancer stem cells (CSCs), and targeting UHRF1 can effectively inhibit tumor initiation and CSC self-renewal. Through regulating the CEBPA and Hedgehog signaling pathway, UHRF1 deficiency induces cancer cell differentiation and suppression. These findings have important implications for the development of therapeutic strategies for hepatocellular carcinoma (HCC).
CELL DEATH & DISEASE
(2023)
Review
Oncology
Si-yu Chen, Jin-long Cao, Kun-peng Li, Shun Wan, Li Yang
Summary: BIN1 protein has various physiological functions and is closely associated with the development of many diseases. Recent findings have revealed the potential mechanisms of BIN1 in cancer development and its feasibility as a prognostic marker and therapeutic target.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Cell Biology
Amelie Massemin, Delphine Goehrig, Jean-Michel Flaman, Sara Jaber, Audrey Griveau, Sophia Djebali, Elisabeth Marcos, Lea Payen, Jacqueline Marvel, Romain Parent, Serge Adnot, Philippe Bertolino, Jennifer Rieusset, Antonin Tortereau, David Vindrieux, David Bernard
Summary: Cellular senescence is caused by various stresses and leads to the accumulation of senescent cells. These cells secrete factors that contribute to age-related alterations and diseases. The pro-senescent receptor PLA2R1 plays a significant role in regulating age-related alterations in mice, and its loss provides protection against the effects of a Western diet.
Article
Cell Biology
Jyh-Der Leu, Chung-Yih Wang, Chia-Chien Lo, Min-Ying Lin, Chun-Yuan Chang, Wen-Chin Hung, Shi-Ting Lin, Bo-Shen Wang, Yi-Jang Lee
Summary: Low dose radiation does not induce apoptosis, but rather induces cell senescence and enhances the migration and invasion of unirradiated cells. The upregulation of c-Myc by low dose radiation plays a key role in inducing cell senescence and enhancing the motility of unirradiated cells.
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)
Article
Respiratory System
Delphine Beaulieu, Aya Attwe, Marielle Breau, Larissa Lipskaia, Elisabeth Marcos, Emmanuelle Born, Jin Huang, Shariq Abid, Genevieve Derumeaux, Amal Houssaini, Bernard Maitre, Marine Lefevre, Nora Vienney, Philippe Bertolino, Sara Jaber, Hiba Noureddine, Delphine Goehrig, David Vindrieux, David Bernard, Serge Adnot
Summary: Cell senescence is an important process in age-related dysfunction and diseases like COPD. The overexpression of PLA2R1 in COPD lungs contributes to senescence characteristics and inflammation, while targeting JAK1/2 may be a promising therapeutic approach for COPD.
EUROPEAN RESPIRATORY JOURNAL
(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
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.