Article
Cell Biology
Boyi Zhang, Qilai Long, Shanshan Wu, Qixia Xu, Shuling Song, Liu Han, Min Qian, Xiaohui Ren, Hanxin Liu, Jing Jiang, Jianming Guo, Xiaoling Zhang, Xing Chang, Qiang Fu, Eric W-F Lam, Judith Campisi, James L. Kirkland, Yu Sun
Summary: Cellular senescence is regulated by histone H3-specific demethylase KDM4, which is associated with changes in H3K9/H3K36 methylation and poorer survival in prostate cancer patients. Targeting KDM4 reduces senescence-associated secretory phenotype (SASP) in stromal cells, promoting cancer cell apoptosis and prolonging survival in experimental animals. This study suggests KDM4 as a key modulator in manipulating cellular senescence and limiting its contribution to age-related pathologies, including cancer.
Review
Cell Biology
Runjiu Zhu, Haoyang Wan, Hong Yang, Mingrui Song, Yu Chai, Bin Yu
Summary: With the increasing proportion of older individuals in most countries, the prevalence of osteoporosis has been on the rise, leading scientists to focus on the pathogenic mechanisms of this condition. In recent years, research on cellular senescence has shed light on the role of the senescent microenvironment in osteoporosis. Senescent cells in the bone marrow secrete senescence-associated secretory phenotype (SASP) factors, which can impact both their own function and the surrounding healthy cells, exacerbating the aging process. The composition of SASP may vary depending on the cause of osteoporosis. This review summarizes the relationship between SASP factors and osteoporosis and provides new insights for the investigation of its mechanism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Oncology
Cecilia R. Chambers, Shona Ritchie, Brooke A. Pereira, Paul Timpson
Summary: Senescence is a cellular state where cells halt the cell cycle in response to stress, with senescent cancer cells and adjacent cells potentially remaining metabolically active and secreting pro-inflammatory factors known as the SASP. The SASP plays a critical role in tumorigenesis, affecting various processes and treatment efficacy. Future research on therapy-induced senescence and pharmacological manipulation may provide new avenues for cancer therapeutics.
MOLECULAR ONCOLOGY
(2021)
Article
Cell Biology
Ryan Wallis, Natasa Josipovic, Hannah Mizen, Arturo Robles-Tenorio, Eleanor J. Tyler, Argyris Papantonis, Cleo L. Bishop
Summary: The secretion of small extracellular vesicles (EVs) by senescent cells is found to play an important role in aging and age-related pathologies. Separating the soluble SASP from the vesicular component helps clarify the functional significance of EVs and provides a framework for future investigations.
JOURNAL OF EXTRACELLULAR VESICLES
(2021)
Review
Immunology
Ziqi Yue, Lulingxiao Nie, Pengfei Zhao, Ning Ji, Ga Liao, Qi Wang
Summary: The senescence-associated secretory phenotype (SASP) is a crucial driver of chronic inflammation and aging phenotypes, and it also plays a role in the pathogenesis of multiple oral diseases. This article used bibliometric analysis to examine the composition of SASP and found that cytokines, growth factors, proteases, lipid metabolites, and extracellular vesicles are the main components. Based on the evidence, a hypothetical framework for the progression of SASP-related oral pathology was proposed, and potential therapies targeting specific SASP factors were suggested.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Angelica Giuliani, Anna Maria Giudetti, Daniele Vergara, Laura Del Coco, Deborah Ramini, Sara Caccese, Matilde Sbriscia, Laura Graciotti, Gianluca Fulgenzi, Luca Tiano, Francesco Paolo Fanizzi, Fabiola Olivieri, Maria Rita Rippo, Jacopo Sabbatinelli
Summary: Cellular senescence is closely linked to endothelial dysfunction, resulting in chronic inflammation and vascular impairments. The metabolic behavior of senescent endothelial cells is complex and plays a role in the proinflammatory phenotype.
Article
Dermatology
Marie-Sophie Narzt, Vera Pils, Christopher Kremslehner, Ionela-Mariana Nagelreiter, Markus Schosserer, Emilia Bessonova, Alina Bayer, Raffaela Reifschneider, Lucia Terlecki-Zaniewicz, Petra Waidhofer-Soellner, Michael Mildner, Erwin Tschachler, Maria Cavinato, Sophia Wedel, Pidder Jansen-Duerr, Lucia Nanic, Ivica Rubelj, Abdoelwaheb El-Ghalbzouri, Samuele Zoratto, Martina Marchetti-Deschmann, Johannes Grillari, Florian Gruber, Ingo Laemmermann
Summary: During aging, skin accumulates senescent cells which play a key role in tissue repair and homeostasis when transiently present. However, the persistence of senescent cells that evade clearance leads to age-related deterioration of the skin. Research suggests that lysophospholipids may contribute to immune evasion and chronic inflammation in skin aging.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Cell Biology
Keren Chen, Junyan Zhang, Feng Liang, Qi Zhu, Shufang Cai, Xian Tong, Zuyong He, Xiaohong Liu, Yaosheng Chen, Delin Mo
Summary: HMGB2 deficiency impedes adipogenesis while overexpression increases adipogenic potential. The HMGB2-C/EBP beta axis plays an important role in mediating adipogenesis and may serve as a potential therapeutic target for obesity.
CELL DEATH & DISEASE
(2021)
Correction
Cell Biology
Remi-Martin Laberge, Yu Sun, Arturo V. Orjalo, Christopher K. Patil, Adam Freund, Lili Zhou, Samuel C. Curran, Albert R. Davalos, Kathleen A. Wilson-Edell, Su Liu, Chandani Limbad, Marco Demaria, Patrick Li, Gene B. Hubbard, Yuji Ikeno, Martin Javors, Pierre-Yves Desprez, Christopher C. Benz, Pankaj Kapahi, Peter S. Nelson, Judith Campisi
Summary: Correction to the paper has been published.
NATURE CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiaojing Du, Xingxing Zhang, Zhuoran Qi, Ziyi Zeng, Ye Xu, Zhijie Yu, Xin Cao, Jinglin Xia
Summary: This study investigated the relationship between the senescence-associated secretory phenotype (SASP) and stemness in intrahepatic cholangiocarcinoma (ICC). The researchers identified senescence-related stemness genes (SRSGs) in ICC and established a classification based on these genes. They also developed a risk score model for ICC and found positive correlations between the risk score, stemness, immune infiltration, metabolism, and oncogenic signatures in ICC. Additionally, the study demonstrated the up-regulation of HELLS, a SRSG, in tumor-repopulating cells with stemness features and its role in colony size, migration, invasion, and SASP in ICC.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Cell Biology
Kelly E. Leon, Raquel Buj, Elizabeth Lesko, Erika S. Dahl, Chi-Wei Chen, Naveen Kumar Tangudu, Yuka Imamura-Kawasawa, Andrew Kossenkov, Ryan P. Hobbs, Katherine M. Aird
Summary: Oncogene-induced senescence (OIS) is a stable cell cycle arrest that occurs in normal cells upon oncogene activation. The expression of DOT1L has been identified as an epigenetic regulator of the SASP, providing a potential strategy to inhibit the negative side effects of senescence while maintaining the beneficial inhibition of proliferation.
JOURNAL OF CELL BIOLOGY
(2021)
Review
Geriatrics & Gerontology
Wen-juan Wang, Xiang-mei Chen, Guang-yan Cai
Summary: Renal fibrosis plays a crucial role in chronic kidney disease, but the complex and unclear pathological process hinders effective treatment. Cellular senescence and the SASP are reported to cause renal fibrosis, and inhibiting them may be a potential strategy for prevention and treatment. Emerging interventions targeting the SASP, caloric restriction and mimetics, as well as novel regeneration therapies with stem cells, show promising therapeutic strategies.
EXPERIMENTAL GERONTOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Barbora Salovska, Alexandra Kondelova, Kristyna Pimkova, Zuzana Liblova, Miroslav Pribyl, Ivo Fabrik, Jiri Bartek, Marie Vajrychova, Zdenek Hodny
Summary: This study reveals a novel role of PRDX6 in senescent cell viability and the development of senescence-associated secretory phenotype (SASP). It highlights the potential of PRDX6 as a drug target for senolytic or senomodulatory therapy.
Review
Cell Biology
Ruchi Kumari, Parmjit Jat
Summary: Cellular senescence is a stable cell cycle arrest triggered in response to various stimuli, characterized by dynamic changes in senescent cells. It has both positive effects on tissue repair and anti-cancer mechanisms, but can also negatively impact organismal health. Multiple pathways, including p53/p21 and p16/pRB, play central roles in regulating this process.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Priyanka Banerjee, Sivareddy Kotla, Loka Reddy Velatooru, Rei J. Abe, Elizabeth A. Davis, John P. Cooke, Keri Schadler, Anita Deswal, Joerg Herrmann, Steven H. Lin, Jun-ichi Abe, Nhat-Tu Le
Summary: Cellular senescence plays a crucial role in the development of cancer and cardiovascular diseases, particularly at the intersection between the two. The senescence-associated secretory phenotype (SASP) of senescent cells is a common factor in both cancer and CVD.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Cell Biology
Shanna L. Bowman, Linh Le, Yueyao Zhu, Dawn C. Harper, Anand Sitaram, Alexander C. Theos, Elena Sviderskaya, Dorothy C. Bennett, Graca Raposo-Benedetti, David J. Owen, Megan K. Dennis, Michael S. Marks
Summary: The vSNARE VAMP7 is sorted into transport carriers in complex with the tSNARE STX13, with sorting requiring recognition by either AP-3 delta or pallidin subunit of BLOC-1, but not both. This mechanism allows for redundant recognition of sorting determinants on a SNARE complex by an AP-3-BLOC-1 super-complex.
JOURNAL OF CELL BIOLOGY
(2021)
Editorial Material
Multidisciplinary Sciences
Aaron Clauset, Kian Behbakht, Benjamin G. Bitler
Article
Oncology
Tomomi M. Yamamoto, Patricia G. Webb, Dana M. Davis, Heidi K. Baumgartner, Elizabeth R. Woodruff, Saketh R. Guntupalli, Margaret Neville, Kian Behbakht, Benjamin G. Bitler
Summary: This study examines the relationship between claudin-4 expression and the response to PARP inhibitors in ovarian cancer tumors. It suggests that claudin-4 expression could serve as both a marker of PARP inhibitor response and a therapeutic target to improve PARP inhibitor response.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Oncology
Brooke E. Sanders, Tomomi M. Yamamoto, Alexandra McMellen, Elizabeth R. Woodruff, Amber Berning, Miriam D. Post, Benjamin G. Bitler
Summary: Identifying novel and durable treatments for HGSOC is crucial for extending patient survival. This study shows that the high expression of DUSP1 is associated with worse prognosis and therapy resistance in HGSOC.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Biochemical Research Methods
Thao Vu, Julia Wrobel, Benjamin G. Bitler, Erin L. Schenk, Kimberly R. Jordan, Debashis Ghosh
Summary: Investigating spatial patterns and interactions of cells in the tumor microenvironment (TME) provides useful insights into cancer development and progression. In this work, we proposed a novel approach which combined established spatial summary functions with functional data analysis to flexibly model the cell-cell interactions with overall survival at different inter-cell distances, in conjunction with other clinical predictors such as age, disease stage. By applying the proposed framework to multiplex immunohistochemistry (mIHC) data of patients with non-small cell lung cancer (NSCLC), we studied the nonlinear impact of spatial interactions between tumor and stromal cells on overall survival. The applicability of our proposed method is further validated using a publicly available multiplexed ion beam imaging (MIBI) triple-negative breast cancer (TNBC) dataset.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Oncology
Alexandra McMellen, Tomomi M. Yamamoto, Lubna Qamar, Brooke E. Sanders, Lily L. Nguyen, Daniela Ortiz Chavez, Jaidev Bapat, Amber Berning, Miriam D. Post, Joshua Johnson, Kian Behbakht, Elmar Nurmemmedov, Edward B. Chuong, Benjamin G. Bitler
Summary: This study identifies a novel p38-ATF6-mediated AP-1 signaling pathway that contributes to PARPi resistance and suggests the potential of combining PARPi and AP-1 signaling inhibitors for treatment.
MOLECULAR CANCER RESEARCH
(2023)
Article
Oncology
Ryne Holmberg, Mikella Robinson, Samuel F. Gilbert, Omar Lujano-Olazaba, Jennifer A. Waters, Emily Kogan, Candyd Lace R. Velasquez, Denay Stevenson, Luisjesus S. Cruz, Logan J. Alexander, Jacqueline Lara, Emily M. Mu, Jared Rafael Camillo, Benjamin G. Bitler, Tom Huxford, Carrie D. House
Summary: Disease recurrence in high-grade serous ovarian cancer may be attributed to resistant cancer stem-like cells (CSC) that can reestablish tumors. The study reveals that the TNF-like weak inducer of apoptosis (TWEAK) and its receptor, Fn14, play a role in activating the alternative NF-xB signaling pathway in ovarian tumors after chemotherapy. Furthermore, TWEAK enhances the characteristics of CSCs and induces the expression of the CSC marker CD117 in ovarian cancer cells. Blocking the TWEAK-Fn14-RelB signaling cascade prolongs survival in a mouse model of ovarian cancer treated with carboplatin chemotherapy.
MOLECULAR CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Tzu-Ting Huang, Sandra Sczerba Burkett, Mayank Tandon, Tomomi M. Yamamoto, Nitasha Gupta, Benjamin G. Bitler, Jung-Min Lee, Jayakumar R. Nair
Summary: Resistance to PARP inhibitors in ovarian cancer can be influenced by treatment strategies and is related to the functionality of BRCA2. Different dosing/timing schemes can lead to the development of distinct resistance mechanisms, including rapid restoration of BRCA2 function and promotion of drug efflux activity, as well as activation of alternative signaling pathways to restore DNA repair and fork stabilization.
Article
Multidisciplinary Sciences
Margaret C. Neville, Patricia G. Webb, Heidi K. Baumgartner, Benjamin G. Bitler
Summary: In this study, the localization of Claudin-4 protein in ovarian tumor cells was investigated. It was found that Claudin-4 is mainly localized in the perinuclear region, plasma membranes, and cytoplasmic puncta, but does not form tight junctions. Additionally, Claudin-4 is mainly localized to the Golgi compartment and is associated with Golgi markers GM130 and plasma membrane receptor Notch2 in dividing cells.
Article
Immunology
Joshua Johnson, So-Youn Kim, Peter Ka Sam, Rengasamy Asokan, Evelyn Llerena Cari, Elise S. S. Bales, Thanh-Ha Luu, Lauren Perez, Amanda N. N. Kallen, Liesl Nel-Themaat, Alex J. J. Polotsky, Miriam D. D. Post, David J. J. Orlicky, Kimberly R. R. Jordan, Benjamin G. G. Bitler
Summary: This study found that PD-1 checkpoint proteins are widely expressed in human ovaries and fallopian tubes, suggesting their involvement in immune regulation during folliculogenesis, the window of ovulation, and the immune-privileged period of eggs and embryos. This is the first study on PD-1 checkpoint proteins in human tubo-ovarian specimens and their potential regulatory action in the contexts of normal and assisted reproduction.
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2023)
Review
Obstetrics & Gynecology
Brooke E. Sanders, Rebecca Wolsky, Elizabeth S. Doughty, Kristen L. Wells, Debashis Ghosh, Lisa Ku, Joseph G. Pressey, Benjamin B. Bitler, Lindsay W. Brubaker
Summary: This article reports a case of small cell carcinoma of the ovary hypercalcemic type (SCCOHT) with both SMARCA4 and BRCA2 germline mutations. The clinical presentation, histopathology, and treatment process are described, along with spatial transcriptomics analysis of the original tumor.
GYNECOLOGIC ONCOLOGY REPORTS
(2022)
Review
Endocrinology & Metabolism
Chandler S. Callaway, Lila M. Mouchantat, Benjamin G. Bitler, Andrea Bonetto
Summary: Cancer-associated cachexia is a common occurrence in cancer patients, including those with ovarian cancer. Reduced skeletal muscle mass in ovarian cancer patients is associated with worse outcomes. Mouse models show characteristics of cachexia in ovarian cancer, but there is limited research on ovarian cancer-associated cachexia compared to other cancer types. Certain soluble factors may serve as therapeutic targets for mitigating cachexia in ovarian cancer. However, more research is needed to determine the translational relevance of these findings due to the relatively low number of studies.
Article
Biotechnology & Applied Microbiology
Jaidev Bapat, Tomomi M. Yamamoto, Elizabeth R. Woodruff, Lubna Qamar, Railey G. Mikeska, Katherine M. Aird, Zachary L. Watson, Lindsay W. Brubaker, Benjamin G. Bitler
Summary: Ovarian cancer, especially the high grade serous ovarian carcinoma (HGSC) subtype, is highly lethal. Previous research has identified CASC4 gene as a driver of anoikis resistance in HGSC cells. In this study, the researchers provide further evidence of the importance of CASC4 in ovarian cancer development and demonstrate its role in mediating the modification of membrane-associated proteins, which promotes the survival and dissemination of HGSC.
CANCER GENE THERAPY
(2023)
Article
Oncology
Heng Liu, Jianhuang Lin, Wei Zhou, Renyta Moses, Zhongping Dai, Andrew V. Kossenkov, Ronny Drapkin, Benjamin G. Bitler, Sergey Karakashev, Rugang Zhang
Summary: This study demonstrates that the extent of effector CD8+ T cell infiltration into tumors is influenced by a histone H3 demethylase (KDM5A) in epithelial ovarian cancer. KDM5A inhibits immune cell infiltration and antitumor immune responses by silencing genes involved in antigen processing and presentation. Inhibition of KDM5A restores gene expression in the antigen-presentation pathway and promotes antitumor immune responses mediated by CD8+ T cells.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Oncology
Brooke E. Sanders, Lisa Ku, Paul Walker, Benjamin G. Bitler
Summary: The study analyzed molecular tumor profiling data from 18 patients diagnosed with primary serous ovarian cancer. Results showed that BRCA genetic variants were more likely to be identified in plasma, and there were variations in the frequency of co-occurring genetic variants across different biocompartments.
TECHNOLOGY IN CANCER RESEARCH & TREATMENT
(2021)
