The basic helix-loop-helix transcription factor, HES3, acts downstream of the PAX3-FOXO1 fusion oncogene to impair muscle differentiation and promote tumorigenesis in rhabdomyosarcoma, a childhood muscle cancer.
In fusion-positive rhabdomyosarcoma, CHD4 positively regulates super-enhancer-mediated gene expression by allowing a chromatin architecture at these cis-regulatory regions, which is permissive to the binding of the transcription factor PAX3-FOXO1.
Syngeneic tp53-null zebrafish develop a wide range of tumors that engraft into recipient animals with loss of Tp53 leading to increased metastasis in embryonal rhabdomyosarcoma (ERMS), likely accounting for increased aggression in TP53-inactivated human ERMS.
MYF5 and MYOD regulate rhabdomyosaroma growth and tumor-propagating potential, acting more than as passive markers retained from the target cell-of-origin during transformation.
The functional relevance of stem cell niche perturbation in sarcomagenesis is defined and the mouse model presented provides a rationale for the use of combination therapy for the treatment of genetically heterogeneous sarcomas.
The availability of asparagine is important for cell growth and nascent peptide synthesis in certain sarcoma cells, and could be targeted therapeutically to inhibit tumor growth.
BRD9 provides the first actionable therapeutic target in synovial sarcoma tumours that is both biochemically and functionally linked to the SS18-SSX fusion protein which drives disease development.
The IGF2 mRNA binding protein-2/IMP2, overexpressed in many common cancers, drives cancer cell proliferation by increasing the abundance of IGF2 and the oncogene HMGA1, which controls a network of effectors that enhance IGF2 action.