Article
Biochemistry & Molecular Biology
Diwei Zheng, Weihai Liu, Wenlin Xie, Guanyu Huang, Qiwei Jiang, Yang Yang, Jiarong Huang, Zihao Xing, Mengling Yuan, Mengning Wei, Yao Li, Junqiang Yin, Jingnan Shen, Zhi Shi
Summary: The study revealed that AHA1 is significantly overexpressed in osteosarcoma, associated with prognosis, and promotes tumor growth and metastasis. AHA1 upregulates metabolic activity to meet cellular energy needs and is positively correlated with IDH1 protein. High IDH1 level is also linked to poor prognosis.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Oncology
Qizhi Qin, Mario Gomez-Salazar, Robert J. Tower, Leslie Chang, Carol D. Morris, Edward F. McCarthy, Kang Ting, Xinli Zhang, Aaron W. James
Summary: The study reveals that NELL1, a secreted glycoprotein, plays a crucial role in sarcoma progression and prognosis by modulating cell invasion potential. Deletion of NELL1 significantly reduces metastasis and disease progression in osteosarcoma, both in human and mouse models. Further analysis shows that NELL1 loss alters the expression of matricellular proteins associated with cell signaling.
Article
Biotechnology & Applied Microbiology
Luoying Li, Yifan Zhang, Yan Gao, Yaqi Hu, Rui Wang, Shuwen Wang, Yuanyang Li, Yumin He, Chengfu Yuan
Summary: Osteosarcoma (OS) is the most common primary osseous malignant tumor in adolescents and children. The standard therapy involves surgery combined with neoadjuvant/post-surgery chemotherapy, but chemoresistance often leads to poor efficacy. In this study, the upregulation of lncRNA SNHG14 was found to contribute to treatment resistance by suppressing ferroptosis in a nutlin3a-resistant OS cell line. Knockdown of lncRNA SNHG14 reversed drug resistance and activated ferroptosis, indicating its role in chemotherapy resistance and ferroptosis inhibition. Targeting lncRNA SNHG14 may provide a new approach to overcome drug resistance and improve treatment efficacy in osteosarcoma.
CANCER GENE THERAPY
(2023)
Article
Oncology
Shu-fan Ji, Sheng-Lian Wen, Yu Sun, Pi-Wei Huang, Hao Wu, Mao-lin He
Summary: STIL is closely associated with the proliferation and invasion of osteosarcoma, and may promote the progression of osteosarcoma by regulating the expression of key genes such as CDK1, CCNB2, CDC20, CCNA2, BUB1, and AURKB.
CANCER CELL INTERNATIONAL
(2021)
Article
Multidisciplinary Sciences
Valeriia Gulaia, Mikhail Shmelev, Aleksander Romanishin, Nikita Shved, Vladislav Farniev, Nikolay Goncharov, Arthur Biktimirov, Irene Lisa Vargas, Konstantin Khodosevich, Alexander Kagansky, Vadim Kumeiko
Summary: This study characterized rare subpopulations of glioma stem cells (GSCs) with IDH1 and TP53 mutations using single-nucleus transcriptomics. It was found that double-mutant GSCs showed a commitment to highly invasive oligodendrocyte- and astroglia-like progenitors. These GSCs also exhibited upregulated markers related to collagen synthesis, altered lipogenesis, and high migration. The findings suggest potential treatment targets for different subtypes of gliomas.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Takatsune Shimizu, Eiji Sugihara, Hideyuki Takeshima, Hiroyuki Nobusue, Rui Yamaguchi, Sayaka Yamaguchi-Iwai, Yumi Fukuchi, Toshikazu Ushijima, Akihiro Muto, Hideyuki Saya
Summary: Mutant p53 in osteosarcoma cells does not suppress the activity of wild-type p53. Targeting mutant p53 R270C (equivalent to human R273C) has limited therapeutic potential, as it does not prevent invasion and metastasis in cells.
Article
Biochemistry & Molecular Biology
Shohei Otani, Yuki Date, Tomoya Ueno, Tomoko Ito, Shuhei Kajikawa, Keisuke Omori, Ichiro Taniuchi, Masahiro Umeda, Toshihisa Komori, Junya Toguchida, Kosei Ito
Summary: This study found that the deficiency of p53 promotes osteosarcomagenesis in both human and mouse by allowing Runx3 to induce oncogenic Myc expression. Reduction of Myc levels by disrupting mR1 or knocking down Runx3 can decrease tumorigenicity in p53-deficient OS cells and effectively suppress OS development in OS mice. Furthermore, Runx inhibitors have therapeutic effects on OS mice.
Article
Biochemistry & Molecular Biology
Keisuke Omori, Shohei Otani, Yuki Date, Tomoya Ueno, Tomoko Ito, Masahiro Umeda, Kosei Ito
Summary: Osteosarcoma is a disease in humans characterized by TP53 mutations. In mice, loss of p53 triggers OS development, and osteoprogenitor-specific p53-deleted mice are widely used to study the process of osteosarcomagenesis. However, the molecular mechanisms underlying the initiation or progression of OS following or parallel to p53 inactivation remain largely unknown. This study reveals a novel tumor suppressive mechanism mediated by C/ebp alpha in p53-deficient osteosarcomagenesis, highlighting the importance of the Runx-Myc oncogenic axis as a therapeutic target for OS.
Article
Multidisciplinary Sciences
Arata Matsuyama, Geoffrey A. Wood, Rachael Speare, Courtney R. Schott, Anthony J. Mutsaers
Summary: The study revealed that dogs with osteosarcoma had higher levels of uPA in serum and most tissues expressed uPA and uPAR, indicating autocrine/paracrine activation of the pathway. High serum uPA level was associated with shorter progression-free survival, potentially serving as a prognostic biomarker for canine osteosarcoma.
Article
Clinical Neurology
C. Mircea S. Tesileanu, Wies R. Vallentgoed, Marc Sanson, Walter Taal, Paul M. Clement, Wolfgang Wick, Alba Ariela Brandes, Jean Francais Baurain, Olivier L. Chinot, Helen Wheeler, Sanjeev Gill, Matthew Griffin, Leland Rogers, Roberta Ruda, Michael Weller, Catherine McBain, Jaap Reijneveld, Roelien H. Enting, Francesca Caparrotti, Thierry Lesimple, Susan Clenton, Anja Gijtenbeek, Elizabeth Lim, Filip de Vos, Paul J. Mulholland, Martin J. B. Taphoorn, Iris de Heer, Youri Hoogstrate, Maurice de Wit, Lorenzo Boggiani, Sanne Venneker, Jan Oosting, Judith V. M. G. Bovee, Sara Erridge, Michael A. Vogelbaum, Anna K. Nowak, Warren P. Mason, Johan M. Kros, Pieter Wesseling, Ken Aldape, Robert B. Jenkins, Hendrikus J. Dubbink, Brigitta Baumert, Vassilis Golfinopoulos, Thierry Gorlia, Martin van den Bent, Pim J. French
Summary: Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are common in various tumor types, with gliomas showing a particularly high frequency of the IDH1(R132H) mutation. Patients with IDH1(R132H) mutations tend to have lower DNA methylation levels and higher gene expression compared to other IDH1/2 mutations. The different prognosis between IDH1(R132H) mutated astrocytomas and non-R132H IDH1/2-mutated astrocytomas highlights the clinical relevance of distinct IDH mutations.
ACTA NEUROPATHOLOGICA
(2021)
Article
Cell Biology
Bing Li, Xiaoqian Dang, Jiafeng Duan, Guangyang Zhang, Jia Zhang, Qichun Song
Summary: This study found that SIX4 is overexpressed in osteosarcoma and is associated with poor prognosis. SIX4 promotes osteosarcoma progression by upregulating isocitrate dehydrogenase 1 (IDH1), providing novel prognostic biomarkers and potential therapeutic targets for osteosarcoma patients.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2023)
Article
Chemistry, Applied
Zhen Pan, Dong-dong Cheng, Xiao-juan Wei, Shi-jie Li, Hua Guo, Qing-cheng Yang
Summary: The study revealed that Chitooligosaccharide (COS) has anti-tumor activity against osteosarcoma cells by inducing apoptosis and autophagy through the p53/mTOR signaling pathway. COS also inhibits tumor growth and metastasis, as well as increases sensitivity to chemotherapy.
CARBOHYDRATE POLYMERS
(2021)
Article
Multidisciplinary Sciences
Xueqin Chen, Jun Liu, Yuqin Li, Yuequan Zeng, Fang Wang, Zexiong Cheng, Hao Duan, Guopeng Pan, Shangqi Yang, Yuling Chen, Qing Li, Xi Shen, Ying Li, Zixi Qin, Jiahong Chen, Youwei Huang, Xiangyu Wang, Yuli Lu, Minfeng Shu, Yubo Zhang, Guocai Wang, Kai Li, Xi Lin, Fan Xing, Haipeng Zhang
Summary: IDH1 mutation inhibits antiviral interferon responses in glioma cells and confers sensitivity to oncolytic virotherapy.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Shirley Chu, Zachary L. Skidmore, Jason Kunisaki, Jason R. Walker, Malachi Griffith, Obi L. Griffith, Jeffrey N. Bryan
Summary: Osteosarcoma is rare in children but common in adult large breed dogs. Mutational landscape varies between dogs, but chromosomal lesions were the most common type of mutation. Mutational profiling of individual patients with canine OSA is recommended prior to targeted therapy due to the observed heterogeneity.
Article
Oncology
Stephanie C. Wu, Ahhyun Kim, Yijun Gu, Daniel I. Martinez, Loredana Zocchi, Claire C. Chen, Jocelyne Lopez, Kelsey Salcido, Sarah Singh, Jie Wu, Ali Nael, Claudia A. Benavente
Summary: Loss-of-function mutations at the RB1 gene worsen clinical outcomes in osteosarcoma. The study has identified UHRF1 as an important downstream effector of the RB/E2F signaling pathway that promotes cell proliferation, migration, invasion, angiogenesis, and metastasis in osteosarcoma. UHRF1 overexpression suppresses AMPK activation and SEMA3E expression, leading to increased angiogenesis. Additionally, UHRF1 affects the expression of extracellular vesicles and their cargo, including uPA, contributing to migration and metastasis. Knocking out Uhrf1 in a mouse model shows decreased metastasis and improved survival in RB1 loss-associated osteosarcoma.
