Article
Biology
Carla Regina, Ebrahem Hamed, Geoffroy Andrieux, Sina Angenendt, Michaela Schneider, Manching Ku, Marie Follo, Marco Wachtel, Eugene Ke, Ken Kikuchi, Anton G. Henssen, Beat W. Schafer, Melanie Boerries, Amy J. Wagers, Charles Keller, Simone Hettmer
Summary: The study shows that heterogeneous expression of PAX3:FOXO1 at the single cell level in rhabdomyosarcoma cells may provide a critical advantage during tumor progression.
LIFE SCIENCE ALLIANCE
(2021)
Article
Biochemistry & Molecular Biology
Qiande Hu, Liang Zhu, Yuan Li, Jianjun Zhou, Jun Xu
Summary: The study revealed that PAX3-FOXO1 inhibits ACTA1 expression at transcription and protein levels through the RhoA-MKL1-SRF signaling pathway, which may contribute to the tumorigenesis and development of ARMS. Overexpression of ACTA1 in RH30 cells was shown to inhibit cell proliferation and migration in vitro and impair tumor growth in vivo compared to the control groups.
CELL AND BIOSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Susu Zhang, Jing Wang, Qi Liu, W. Hayes McDonald, Monica L. Bomber, Hillary M. Layden, Jacob Ellis, Scott C. Borinstein, Scott W. Hiebert, Kristy R. Stengel
Summary: Transcriptional control is a dynamic process that is challenging to study using traditional genetic methods. In this study, we used a chemical-genetic approach to quickly degrade the transcriptional activator PAX3-FOXO1 and investigated its mechanism of action. Our findings revealed that PAX3-FOXO1 is involved in regulating gene expression and maintaining chromatin accessibility and enhancer architecture.
Article
Genetics & Heredity
Line J. Manceau, Julien E. Richard Albert, Pier-Luigi J. Lollini, Maxim V. C. E. Greenberg, Pascale J. Gilardi-Hebenstreit, Vanessa E. Ribes
Summary: The chimeric proteins PAX3-FOXO1 and PAX7-FOXO1, derived from chromosomal translocations, exhibit distinct genomic occupancy and transcriptional activity, leading to different pathological manifestations in alveolar rhabdomyosarcoma.
Article
Oncology
Christine M. Heske, Yueh-Yun Chi, Rajkumar Venkatramani, Minjie Li, Michael A. Arnold, Roshni Dasgupta, Susan M. Hiniker, Douglas S. Hawkins, Leo Mascarenhas
Summary: In patients with localized, FOXO1 fusion-positive RMS, clinical factors such as age at diagnosis and tumor size can impact survival outcomes, with older age and larger tumors being adverse prognostic factors for EFS. Patients with both older age and large tumor size experience significantly inferior outcomes.
Correction
Biotechnology & Applied Microbiology
Johanna Pruller, Isabella Hofer, Massimo Ganassi, Philipp Heher, Michelle T. Ma, Peter S. Zammit
Summary: The paper has been amended and the revised version can be accessed through a link at the top of the paper.
CANCER GENE THERAPY
(2021)
Article
Pharmacology & Pharmacy
Xinhua Huang, Jing Liu, Hong Xie
Summary: In this study, propofol was found to suppress cell proliferation, migration, and invasion of osteosarcoma cells through the FOXO1/TUSC7 axis by regulating the AKT/GSK3 beta signaling pathway.
JOURNAL OF PHARMACY AND PHARMACOLOGY
(2021)
Article
Cell Biology
Shivendra Singh, Ahmed Abu-Zaid, Hongjian Jin, Jie Fang, Qiong Wu, Tingting Wang, Helin Feng, Waise Quarni, Ying Shao, Lily Maxham, Alireza Abdolvahabi, Mi-Kyung Yun, Sivaraja Vaithiyalingam, Haiyan Tan, John Bowling, Victoria Honnell, Brandon Young, Yian Guo, Richa Bajpai, Shondra M. Pruett-Miller, Gerard C. Grosveld, Mark Hatley, Beisi Xu, Yiping Fan, Gang Wu, Eleanor Y. Chen, Taosheng Chen, Peter W. Lewis, Zoran Rankovic, Yimei Li, Andrew J. Murphy, John Easton, Junmin Peng, Xiang Chen, Ruoning Wang, Stephen W. White, Andrew M. Davidoff, Jun Yang
Summary: This study identifies KDM4B as a therapeutic vulnerability for PAX3-FOXO1(+) RMS. Inhibition of KDM4B delays tumor growth and suppresses the expression of core oncogenic transcription factors, causing epigenetic alterations of PAX3-FOXO1-governed superenhancers.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Daniela Di Carlo, Cyrus Chargari, Jean-Yves Scoazec, Sophie Cotteret, Arthur Felix, Salma Moalla, Stephane Temam, Veronique Minard-Colin
Summary: Alveolar rhabdomyosarcoma (ARMS) is commonly associated with PAX3/PAX7-FOXO1 fusion gene, but some tumors without this fusion may have new molecular alterations. A rare case of PAX3-NCOA1 ARMS in a two-year-old girl with tongue and nodal extension was treated with a combination of therapies to preserve oral function and minimize long-term effects. International collaboration is necessary to evaluate the prognostic value of this variant fusion in ARMS.
PEDIATRIC BLOOD & CANCER
(2021)
Article
Oncology
Nada Ragab, Julia Bauer, Anja Uhmann, Alexander Marx, Heidi Hahn, Katja Simon-Keller
Summary: Rhabdomyosarcoma (RMS) is an aggressive soft tissue malignancy that mainly affects children. The WNT5A ligand of the non-canonical WNT signaling pathway has been found to have tumor suppressive functions in ERMS and ARMS, decreasing proliferation, migration, self-renewal capacity, and stem cell marker expression of RMS cells. Additionally, WNT5A influences the levels of muscle differentiation markers and destabilizes active beta-Catenin in RMS cells.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2022)
Article
Genetics & Heredity
Huajie Mao, Ya Zhao, Li Lei, Yanxia Hu, Hangrui Zhu, Runzhi Wang, Dongsheng Ni, Jianing Liu, Lei Xu, Hua Xia, Zaikuan Zhang, Meng Ma, Zheng Pan, Qin Zhou, Yajun Xie
Summary: SELS is highly expressed in clear cell renal cell carcinoma (ccRCC) and associated with multiple pathological features. SELS overexpression promotes cell proliferation and inhibits apoptosis, while silence of SELS has the opposite effect. Mechanistically, SELS activates AKT/GSK3 beta/NF-kappa B signaling pathway to enhance cell proliferation and inhibit apoptosis, and stabilizes c-Myc by preventing ubiquitin-proteasome-mediated degradation. Furthermore, SELS inhibits ccRCC cell migration likely through repressing epithelial-mesenchymal transition (EMT).
Article
Biochemistry & Molecular Biology
Alvaro Centron-Broco, Francesca Rossi, Chiara Grelloni, Raffaele Garraffo, Dario Dattilo, Andrea Giuliani, Gaia Di Timoteo, Alessio Colantoni, Irene Bozzoni, Manuel Beltran Nebot
Summary: In this study, a circular RNA called circAFF1 was found to be overexpressed in alveolar rhabdomyosarcoma. Depletion of circAFF1 was shown to affect cell homeostasis and promote cell migration through the downregulation of genes involved in cell adhesion pathways. These findings highlight the potential of circAFF1 as a future therapeutic target for alveolar rhabdomyosarcoma.
Article
Multidisciplinary Sciences
Sara G. Danielli, Ermelinda Porpiglia, Andrea J. De Micheli, Natalia Navarro, Michael J. Zellinger, Ingrid Bechtold, Samanta Kisele, Larissa Volken, Joana G. Marques, Stephanie Kasper, Peter K. Bode, Anton G. Henssen, Dennis Guergen, Olivier Delattre, Didier Surdez, Josep Roma, Peter Buhlmann, Helen M. Blau, Marco Wachtel, Beat W. Schafer
Summary: This study investigates the cellular hierarchy and mechanisms underlying the aggressiveness, chemoresistance, and progression of alveolar rhabdomyosarcoma (aRMS), a pediatric cancer. The researchers identify plastic muscle stem-like cells and cycling progenitors in aRMS that drive tumor growth, as well as a subpopulation of differentiated cells with better outcomes. Chemotherapy eliminates cycling progenitors but enriches aRMS for muscle stem-like cells. The researchers discover a combination of RAF and MEK inhibitors that induce myogenic differentiation and inhibit tumor growth, suggesting the RAS pathway as a promising therapeutic target.
Article
Oncology
Thomas Raze, Eve Lapouble, Brigitte Lacour, Sandra Guissou, Anne-Sophie Defachelles, Nathalie Gaspar, Olivier Delattre, Gaelle Pierron, Emmanuel Desandes
Summary: This study aimed to evaluate the impact of PAX-FOXO1 gene alterations on clinical outcomes in childhood and adolescence patients with ARMS. The study found that patients with PAX3-FOXO1 positive expression were older, had higher metastasis rates, and lower 5-year survival rates. Compared to patients with PAX7-FOXO1 positive and PAX-FOXO1 negative tumors, patients with PAX3-FOXO1 positive tumors had a higher risk of death.
PEDIATRIC BLOOD & CANCER
(2023)
Article
Biotechnology & Applied Microbiology
Soeren S. Huettner, Henriette Henze, Dana Elster, Philipp Koch, Ursula Anderer, Bjoern von Eyss, Julia von Maltzahn
Summary: The expression levels of the transcriptional repressor TRPS1 are specifically enhanced in the embryonal subtype of rhabdomyosarcoma, resulting in impaired myogenic differentiation and tumor growth. Reduction of TRPS1 levels may be a therapeutic approach to drive embryonal rhabdomyosarcoma cells into myogenic differentiation.