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?-catenin stabilization enhances SS18-SSX2-driven synovial sarcomagenesis and blocks the mesenchymal to epithelial transition.


ABSTRACT: ?-catenin is a master regulator in the cellular biology of development and neoplasia. Its dysregulation is implicated as a driver of colorectal carcinogenesis and the epithelial-mesenchymal transition in other cancers. Nuclear ?-catenin staining is a poor prognostic sign in synovial sarcoma, the most common soft-tissue sarcoma in adolescents and young adults. We show through genetic experiments in a mouse model that expression of a stabilized form of ?-catenin greatly enhances synovial sarcomagenesis. Stabilization of ?-catenin enables a stem-cell phenotype in synovial sarcoma cells, specifically blocking epithelial differentiation and driving invasion. ?-catenin achieves its reprogramming in part by upregulating transcription of TCF/LEF target genes. Even though synovial sarcoma is primarily a mesenchymal neoplasm, its progression towards a more aggressive and invasive phenotype parallels the epithelial-mesenchymal transition observed in epithelial cancers, where ?-catenin's transcriptional contribution includes blocking epithelial differentiation.

SUBMITTER: Barrott JJ 

PROVIDER: S-EPMC4673197 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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β-catenin stabilization enhances SS18-SSX2-driven synovial sarcomagenesis and blocks the mesenchymal to epithelial transition.

Barrott Jared J JJ   Illum Benjamin E BE   Jin Huifeng H   Zhu Ju-Fen JF   Mosbruger Tim T   Monument Michael J MJ   Smith-Fry Kyllie K   Cable Matthew G MG   Wang Yanliang Y   Grossmann Allie H AH   Capecchi Mario R MR   Jones Kevin B KB  

Oncotarget 20150901 26


β-catenin is a master regulator in the cellular biology of development and neoplasia. Its dysregulation is implicated as a driver of colorectal carcinogenesis and the epithelial-mesenchymal transition in other cancers. Nuclear β-catenin staining is a poor prognostic sign in synovial sarcoma, the most common soft-tissue sarcoma in adolescents and young adults. We show through genetic experiments in a mouse model that expression of a stabilized form of β-catenin greatly enhances synovial sarcomage  ...[more]

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