Article
Oncology
Shan Wang, Xiaofang Huo, Yiping Yang, Yingxi Mo, Rahul K. Kollipara, Ralf Kittler
Summary: The deubiquitinase USP9X stabilizes EWS-FLI1 protein expression in Ewing sarcoma, and its inhibitor WP1130 can rapidly degrade EWS-FLI1 and inhibit the growth of Ewing sarcoma cells and tumors.
Review
Cell Biology
Maryne Dupuy, Francois Lamoureux, Mathilde Mullard, Anais Postec, Laura Regnier, Marc Baud'huin, Steven Georges, Benedicte Brounais-Le Royer, Benjamin Ory, Francoise Redini, Franck Verrecchia
Summary: Ewing sarcoma (ES) is the second most common primary malignant bone tumor in children, adolescents, and young adults in Europe, with a survival rate of 70% for localized forms using conventional treatment. However, resistance to chemotherapy and pulmonary metastases greatly reduce the survival rate. ES is characterized by a chromosomal translocation that leads to the fusion protein EWS-FLI1, which plays a crucial role in the development of ES. This review provides an overview of ES from a clinical and biological perspective.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Siyuan Su, Jianfeng Chen, Yao Jiang, Ying Wang, Tamara Vital, Jiaming Zhang, Christian Laggner, Kong T. Nguyen, Zhichuan Zhu, Alex W. Prevatte, Natalie K. Barker, Laura E. Herring, Ian J. Davis, Pengda Liu
Summary: Chromosomal translocation leads to the formation of the EWS-FLI1 fusion oncogene in Ewing sarcoma, with SPOP identified as the E3 ligase and OTUD7A as the deubiquitinase regulating EWS-FLI1 protein stability. Targeting OTUD7A with the inhibitor 7Ai shows potential as a therapeutic strategy for Ewing sarcoma dependent on EWS-FLI1 and related fusions.
Review
Biochemistry & Molecular Biology
Muhammad Yasir, Jinyoung Park, Wanjoo Chun
Summary: Despite their clonal origins, tumors evolve into complex communities with phenotypically different cell subpopulations. Ewing sarcoma, a highly aggressive malignancy primarily affecting adolescents, exhibits significant variations in transcriptional activity among tumors despite originating from a common driver mutation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Helong Gong, Busheng Xue, Jinlong Ru, Guoqing Pei, Yan Li
Summary: Ewing sarcoma (EwS) is a rare and predominantly pediatric malignancy of bone and soft tissue in children and adolescents. The EWS-FLI1 oncogene acts as an aberrant transcription factor that drives the cellular transformation of EwS. Direct pharmacological targeting of EWS-FLI1 is difficult, but targeting the EWS-FLI1 protein complex or downstream pathways provides additional therapeutic options.
Review
Oncology
Mingli Li, Chunwei Chen
Summary: Ewing sarcoma (EwS) is a common type of bone and soft tissue cancer that primarily affects children and adolescents. The current treatment approach for EwS patients involves a combination of surgery, radiation, and chemotherapy. However, little progress has been made in the treatment of patients with metastatic or relapsed diseases. Furthermore, the survival rates for localized cases are relatively low, and the development of metastatic tumors significantly reduces the five-year survival rates. Therefore, understanding the regulatory mechanism of EwS tumor metastasis is crucial for developing effective treatment strategies. This review discusses the molecular signatures and heterogeneity associated with EwS metastasis.
Article
Oncology
April A. Apfelbaum, Feinan Wu, Allegra G. Hawkins, Brian Magnuson, Jennifer A. Jime, Sean D. Taylor, Emma D. Wrenn, Olivia Waltner, Elise R. Pfaltzgraff, Jane Y. Song, Cody Hall, Deneen M. Wellik, Mats Ljungman, Scott N. Furlan, Russell J. H. Ryan, Jay F. Sarthy, Elizabeth R. Lawlor
Summary: This study reveals the regulatory role of HOXD13 in EWS::FLI1 transcriptional activity and its impact on the transition of Ewing sarcoma cells towards a mesenchymal state. The findings provide important insights into the progression mechanism of Ewing sarcoma.
CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Hyewon Park, Haeyoung Kim, Victoria Hassebroek, Yoshiaki Azuma, Chad Slawson, Mizuki Azuma
Summary: The study demonstrates that EWSR1/FLI1 induces aneuploidy by interfering with the localization of Aurora B kinase, with phosphorylation of Thr 79 being critical for this process.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Oncology
Saint T. Cervera, Carlos Rodriguez-Martin, Enrique Fernandez-Tabanera, Raquel M. Melero-Fernandez de Mera, Matias Morin, Sergio Fernandez-Penalver, Maria Iranzo-Martinez, Jorge Amhih-Cardenas, Laura Garcia-Garcia, Laura Gonzalez-Gonzalez, Miguel Angel Moreno-Pelayo, Javier Alonso
Summary: Ewing sarcoma is an aggressive bone cancer affecting children and young adults, characterized by chromosomal translocations producing chimeric oncogenic transcription factors. In this study, genetic inactivation of the EWSR1-FLI1 oncogene using CRISPR/Cas9 technology in Ewing sarcoma cells effectively blocked cell proliferation and induced a senescence phenotype. This suggests that complete inactivation of EWSR1-FLI1 at the cellular level could be a promising therapeutic approach in the future.
Article
Oncology
Yu Wang, Hengtang Mai, Ying Yuan, Hairen Chen, Song Wu, Xiang Hu, Aixi Yu
Summary: Ewing sarcoma is an aggressive pediatric tumor with limited diagnostic tools. A near-infrared fluorescent probe targeting the specific fusion protein EWS-FLI1 was synthesized, showing promising results in identifying tumor boundaries and lymph node metastases in animal models. This probe has the potential for early diagnosis and surgical guidance of Ewing sarcoma through molecularly targeted NIR imaging.
MOLECULAR ONCOLOGY
(2021)
Article
Oncology
Alessandra De Feo, Laura Pazzaglia, Lisa Ciuffarin, Fabio Mangiagli, Michela Pasello, Elisa Simonetti, Evelin Pellegrini, Cristina Ferrari, Giuseppe Bianchi, Benedetta Spazzoli, Katia Scotlandi
Summary: Ewing's sarcoma, a common pediatric bone tumor, relies on genetic and epigenetic alterations that induce gene expression reprogramming. The study identifies miR-214-3p as a common mediator of EWS-FLI1 and CD99, and its restoration inhibits tumor cell growth and migration by repressing HMGA1 expression.
Review
Oncology
Ajay Gupta, Richard F. Riedel, Chirag Shah, Scott C. Borinstein, Michael S. Isakoff, Rashmi Chugh, Jeremy M. Rosenblum, Erin S. Murphy, Shauna R. Campbell, Catherine M. Albert, Stacey Zahler, Stefanie M. Thomas, Matteo Trucco
Summary: Ewing sarcoma is a common malignant tumor in adolescents and young adults. This review focuses on the experience of the National Ewing Sarcoma Tumor Board and aims to provide guidelines and recommendations for the upfront management of Ewing sarcoma patients.
Article
Oncology
Rachael Windsor, Anthony Hamilton, Anne McTiernan, Palma Dileo, Maria Michelagnoli, Beatrice Seddon, Sandra J. Strauss, Jeremy Whelan
Summary: This study retrospectively reviewed patients with primary refractory or recurrent Ewing sarcoma and found that high-dose therapy (HDT) is associated with better outcomes compared to non-HDT chemotherapy. The study also developed a prognostic risk score to aid clinical decision-making.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Genetics & Heredity
Runzhi Huang, Dan Huang, Siqiao Wang, Shuyuan Xian, Yifan Liu, Minghao Jin, Xinkun Zhang, Shaofeng Chen, Xi Yue, Wei Zhang, Jianyu Lu, Huizhen Liu, Zongqiang Huang, Hao Zhang, Huabin Yin
Summary: Through systematic bioinformatics analysis, this study revealed the key regulatory network of Ewing sarcoma, which includes DEeRNAs, DETGs, DETFs, immune cells, immune gene sets, and hallmarks of cancer. Additionally, potential small molecules targeting Ewing sarcoma were also identified. The results of this study indicate that PHLDA1 plays a crucial role in the tumorigenesis and progression of Ewing sarcoma.
FRONTIERS IN GENETICS
(2022)
Article
Engineering, Environmental
Govinda Bhattarai, Hyun-Jaung Sim, Han-Sol So, Jeong-Chae Lee, Sung-Ho Kook
Summary: Research has mainly focused on the negative impacts of PM2.5 on respiratory, brain, immune, and metabolic diseases, with little knowledge about its effects on hematopoietic stem cell (HSC) fate. This study investigated the effects of atmospherically relevant PM2.5 on newborn hematopoietic stem progenitor cells (HSPCs), revealing increased oxidative stress and inflammasome activation in the lungs and bone marrow of PM2.5-exposed mice.
JOURNAL OF HAZARDOUS MATERIALS
(2023)
Article
Hematology
Tongjie Wang, Chengxiang Xia, Qitong Weng, Kaitao Wang, Yong Dong, Sha Hao, Fang Dong, Xiaofei Liu, Lijuan Liu, Yang Geng, Yuxian Guan, Juan Du, Tao Cheng, Hui Cheng, Jinyong Wang
Summary: The study reveals a new role for the Nupr1 gene in regulating the quiescence of hematopoietic stem cells (HSC), which can have implications for improving HSC transplantation efficacy. The deletion of the Nupr1 gene activates dormant HSC and provides a competitive advantage in transplantation without compromising their stemness or differentiation capacity. In addition, the inhibition of Nupr1 affects HSC proliferation and engraftment. This finding could contribute to enhancing the success of HSC transplantation.
Article
Hematology
Nan Wang, Jing Yin, Na You, Shangda Yang, Dan Guo, Yangyang Zhao, Yongxin Ru, Xiaoyan Liu, Hui Cheng, Qian Ren, Tao Cheng, Xiaotong Ma
Summary: The transcription factor TWIST1 is identified as a critical regulator of HSC maintenance by modulating mitochondrial function. Deletion of Twist1 leads to decreased HSC frequency, impaired self-renewal capacity, skewed myeloid differentiation, and compromised stress tolerance. The mechanism involves activation of voltage-gated calcium channel Cacna1b, resulting in increased mitochondrial calcium levels, metabolic activity, and reactive oxygen species production, which can be rescued by calcium channel blocker under stress conditions.
Article
Biochemistry & Molecular Biology
Xianwen Ren, Wen Wen, Xiaoying Fan, Wenhong Hou, Bin Su, Pengfei Cai, Jiesheng Li, Yang Liu, Fei Tang, Fan Zhang, Yu Yang, Jiangping He, Wenji Ma, Jingjing He, Pingping Wang, Qiqi Cao, Fangjin Chen, Yuqing Chen, Xuelian Cheng, Guohong Deng, Xilong Deng, Wenyu Ding, Yingmei Feng, Rui Gan, Chuang Guo, Weiqiang Guo, Shuai He, Chen Jiang, Juanran Liang, Yi-min Li, Jun Lin, Yun Ling, Haofei Liu, Jianwei Liu, Nianping Liu, Shu-Qiang Liu, Meng Luo, Qiang Ma, Qibing Song, Wujianan Sun, GaoXiang Wang, Feng Wang, Ying Wang, Xiaofeng Wen, Qian Wu, Gang Xu, Xiaowei Xie, Xinxin Xiong, Xudong Xing, Hao Xu, Chonghai Yin, Dongdong Yu, Kezhuo Yu, Jin Yuan, Biao Zhang, Peipei Zhang, Tong Zhang, Jincun Zhao, Peidong Zhao, Jianfeng Zhou, Wei Zhou, Sujuan Zhong, Xiaosong Zhong, Shuye Zhang, Lin Zhu, Ping Zhu, Bin Zou, Jiahua Zou, Zengtao Zuo, Fan Bai, Xi Huang, Penghui Zhou, Qinghua Jiang, Zhiwei Huang, Jin-Xin Bei, Lai Wei, Xiu-Wu Bian, Xindong Liu, Tao Cheng, Xiangpan Li, Pingsen Zhao, Fu-Sheng Wang, Hongyang Wang, Bing Su, Zheng Zhang, Kun Qu, Xiaoqun Wang, Jiekai Chen, Ronghua Jin, Zemin Zhang
Summary: The study revealed the presence of immune response dysfunction in COVID-19 patients, with different peripheral immune subtype changes associated with clinical features such as age, sex, severity, and disease stages. Additionally, dramatic transcriptomic changes were observed within virus-infected cells, and upregulation of S100A8/A9 in peripheral blood may contribute to the cytokine storms frequently observed in severe patients.
Article
Biotechnology & Applied Microbiology
Mei Zhao, Yi-Dan Sun, Mengdi Yin, Juan-Juan Zhao, Si-Ang Li, Guohua Li, Feng Zhang, Jing Xu, Fei-Ying Meng, Beldon Zhang, Xin-Yu Sun, Jian-Ping Zhang, Tao Cheng, Xiao-Bing Zhang
Summary: This study successfully treated hemophilia A in a mouse model using a gene-editing strategy and identified the humoral immune response as the main cause of decreased treatment efficacy. The findings highlight the importance of modulating the innate immune response triggered by liver damage.
HUMAN GENE THERAPY
(2022)
Article
Oncology
Shengnan Yuan, Xiaomin Wang, Shuaibing Hou, Tengxiao Guo, Yanjie Lan, Shuang Yang, Fei Zhao, Juan Gao, Yuxia Wang, Yajing Chu, Jun Shi, Tao Cheng, Weiping Yuan
Summary: The study indicates that patients with co-mutations of JAK3 and PHF6 have shorter survival times, suggesting a potential role of PHF6 in leukemia progression. Phf6 deficiency promotes JAK3(M511I)-induced T-ALL progression by inhibiting the Bai1-Mdm2-P53 signaling pathway independent of the JAK3/STAT5 signaling pathway. Combination therapy with JAK3 and MDM2 inhibitors may potentially increase the drug benefit for T-ALL patients with PHF6 and JAK3 co-mutations.
Article
Chemistry, Multidisciplinary
Cuicui Liu, Dan Wu, Meijuan Xia, Minmin Li, Zhiqiang Sun, Biao Shen, Yiying Liu, Erlie Jiang, Hongtao Wang, Pei Su, Lihong Shi, Zhijian Xiao, Xiaofan Zhu, Wen Zhou, Qianfei Wang, Xin Gao, Tao Cheng, Jiaxi Zhou
Summary: The study uncovers cellular heterogeneity in adult MKs, identifies an MK subpopulation with high concentration of immune-related genes, and traces the immune signatures of MKs back to the progenitor stage through in vitro research. Additionally, two surface markers for mature MKs with immune characteristics are identified, allowing for rapid response to immune stimuli and potential immune surveillance functions.
Article
Cell Biology
Roger S. Smith, Igor Odintsov, Zebing Liu, Allan Jo-Weng Lui, Takuo Hayashi, Morana Vojnic, Yoshiyuki Suehara, Lukas Delasos, Marissa S. Mattar, Julija Hmeljak, Hillary A. Ramirez, Melissa Shaw, Gabrielle Bui, Alifiani B. Hartono, Eric Gladstone, Siddharth Kunte, Heather Magnan, Inna Khodos, Elisa De Stanchina, Michael P. La Quaglia, Jinjuan Yao, Marick Lae, Sean B. Lee, Lee Spraggon, Christine A. Pratilas, Marc Ladanyi, Romel Somwar
Summary: This study developed preclinical disease models and analyzed expression profiles of DSRCT, identifying EGFR antagonists as potential therapeutic options for DSRCT patients.
DISEASE MODELS & MECHANISMS
(2022)
Article
Oncology
Jinqiang Zhang, Weina Chen, Wenbo Ma, Kyoungsub Song, Sean Lee, Chang Han, Tong Wu
Summary: This study reveals a novel G9a-15PGDH signaling axis that is important in the development and progression of cholangiocarcinoma (CCA). 15-PGDH is epigenetically silenced by G9a, and inhibition of G9a can restore 15-PGDH expression and inhibit CCA cell growth.
MOLECULAR CANCER RESEARCH
(2022)
Article
Oncology
Alifiani Bonita Hartono, Hong-Jun Kang, Lawrence Shi, Whitney Phipps, Nathan Ungerleider, Alexandra Giardina, WeiPing Chen, Lee Spraggon, Romel Somwar, Krzysztof Moroz, David H. Drewry, Matthew E. Burow, Erik Flemington, Marc Ladanyi, Sean Bong Lee
Summary: Desmoplastic Small Round Cell Tumor (DSRCT) is a rare and aggressive malignant cancer caused by a chromosomal translocation. The study identified SIK1 as a direct target of the oncogenic transcription factor EWSR1-WT1, and depletion of SIK1 inhibited tumor cell growth and DNA replication. Combined inhibition of SIK1 and CHEK1 showed enhanced cytotoxicity in DSRCT cells.
Article
Cell Biology
Justin W. Magrath, Hong-Jun Kang, Alifiani Hartono, Madelyn Espinosa-Cotton, Romel Somwar, Marc Ladanyi, Nai-Kong Cheung, Sean B. Lee
Summary: This study found that elevated levels of stemness markers are associated with worse survival and metastasis in DSRCT patients. Additionally, they developed the first in vitro DSRCT CSC model, which showed resistance to chemotherapy. These findings provide important tools for further investigation of the DSRCT subpopulation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Khoa Nguyen, Katherine Hebert, Emily McConnell, Nicole Cullen, Thomas Cheng, Susanna Awoyode, Elizabeth Martin, Weina Chen, Tong Wu, Suresh K. Alahari, Reza Izadpanah, Bridgette M. Collins-Burow, Sean B. Lee, David H. Drewry, Matthew E. Burow
Summary: The liver is an important organ involved in biological functions such as digestion, nutrient storage, and detoxification. It plays an active role in regulating metabolism and is susceptible to hepatocellular carcinoma, which is often associated with chronic inflammation. LKB1 signaling has been found to regulate cellular metabolism and has a tumor suppressive role in many cancers. Using the KMPlotter database, this review correlates RNA levels of LKB1 signaling genes with hepatocellular carcinoma patient survival outcomes and identifies potential biomarkers for clinical use.
PHARMACOLOGICAL RESEARCH
(2023)
Review
Oncology
Khoa Nguyen, Julia Boehling, Minh N. Tran, Thomas Cheng, Andrew Rivera, Bridgette M. Collins-Burow, Sean B. Lee, David H. Drewry, Matthew E. Burow
Summary: Kinases are biomolecules essential for cellular reactions, but disruptions in their expression and activity can lead to diseases like cancer. Though significant progress has been made, a large portion of the human kinome remains understudied. This review focuses on the understudied NEK family of kinases, discussing existing studies, gene expression correlations with patient survival, NEK mutations in different cancer tissues, and potential funding opportunities.
Editorial Material
Cell Biology
Sean B. Lee, Geoffrey Brown
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Khoa Nguyen, Hassan Yousefi, Thomas Cheng, Justin Magrath, Alifiani B. Hartono, Madlin Alzoubi, Katherine Hebert, Courtney K. Brock, Maryl K. Wright, Charles Ethan Byrne, Andrew Rivera, Sam C. Okpechi, Margarite Delores Matossian, Henri Wathieu, Steven Elliott, Mark J. Mondrinos, Sean B. Lee, Bridgette M. Collins-Burow, Suresh K. Alahari, David H. Drewry, Matthew E. Burow
Summary: In this study, we analyzed the expression levels of MAP3K19 in different tissue types using bioinformatics databases, and explored its correlation with patient survival in different cancers.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2022)
Review
Biochemistry & Molecular Biology
Khoa Nguyen, Minh N. Tran, Andrew Rivera, Thomas Cheng, Gabrielle O. Windsor, Abraham B. Chabot, Jane E. Cavanaugh, Bridgette M. Collins-Burow, Sean B. Lee, David H. Drewry, Patrick T. Flaherty, Matthew E. Burow
Summary: The mitogen-activated protein kinasc (MAPK) pathways play crucial roles in cellular signaling and proper biological functions. This review discusses the significance of the MAP3K family in the larger MAPK pathway, their correlation with cancer progression, and the understudied status of these kinases.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2022)
