IGF2 is critical for tumorigenesis by synovial sarcoma oncoprotein SYT-SSX1.
Synovial sarcoma is an aggressive soft tissue tumor characterized by a specific chromosomal translocation between chromosome 18 and X. This translocation can generate a fusion transcript encoding SYT-SSX1, a transforming oncoprotein. We present evidence that SYT-SSX1 induces insulin-like growth factor II expression in fibroblast cells. SYT-SSX2, a fusion also frequently found in synovial sarcoma, is necessary for maintaining Igf2 expression in the synovial sarcoma cell line, and the increased IGF2 synthesis protects cells from anoikis and is required for tumor formation in vivo. We also found a loss of imprinting (LOI) for Igf2 in a limited number of primary synovial sarcomas despite demethylation of CpG dinucleotides critical for maintaining imprinting. These findings suggest that inhibition of the IGF2/IGF1-R signaling pathway may represent a significant therapeutic modality for treating synovial sarcoma.
Sun
Y
Y
Department of Biomedical Genetics Univeristy of Rochester, Rochester, NY 14642, USA. yin_sun@urmc.rochester.edu
Gao
D
D
Liu
Y
Y
Huang
J
J
Lessnick
S
S
Tanaka
S
S
D000818:Animals; D017209:Apoptosis; D018899:CpG Islands; D019175:DNA Methylation; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013584:Sarcoma, Synovial / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015514:Oncogene Proteins, Fusion; C116512:SYT-SSX fusion protein; D007335:Insulin-Like Growth Factor II