NDLI: The SYT-SSX fusion protein and histological epithelial differentiation in synovial sarcoma: relationship with extracellular matrix remodeling

Content Provider	PubMed Central
Author	Saito, Tsuyoshi
Copyright Year	2013
Abstract	Synovial sarcoma (SS) tumor cells, which have the chromosomal translocation t(X;18)(p11.2;q11.2), have an inherently greater propensity for epithelial differentiation than other mesenchymal tumors, especially spindle cell sarcomas. This is caused by de-repression of the transcription of E-cadherin by SYT-SSX1 and SYT-SSX2, which dissociate Snail or Slug, respectively, from the E-cadherin promoter. However, a subset of SS with SYT-SSX1 loses E-cadherin expression despite adequate de-repression because of mutations in E-cadherin, resulting in monophasic histology. The ratio of the expression levels of SYT-SSX1 and Snail is also associated with E-cadherin expression: the lower the SYT-SSX1/Snail ratio, the lower the level of E-cadherin expression, and vice versa, thus affecting tumor histology. In addition, Wnt signal activation caused by mutation of β-catenin, APC, or Axin 1 and 2 is associated with monophasic histology. Remodeling of the extracellular matrix is also important. Only cells that survive all of these steps can finally exhibit biphasic histology. On the other hand, the SYT-SSX2 fusion has a weaker de-repression effect on the E-cadherin promoter than does SYT-SSX1, so it is difficult for SYT-SSX2-expressing tumors to achieve sufficient capacity for epithelial differentiation to form glandular structures. This review provides an interesting model for this epithelial differentiation that shows a possible mechanism for the aberrant mesenchymal to epithelial transition of SS and suggests that it might better be considered an epithelial to mesenchymal transition.
Ending Page	2279
Starting Page	2272
File Format	PDF
ISSN	19362625
e-ISSN	19362625
Journal	International Journal of Clinical and Experimental Pathology
Issue Number	11
Volume Number	6
Language	English
Publisher	e-Century Publishing Corporation
Publisher Date	2013-10-15
Access Restriction	Open
Rights Holder	e-Century Publishing Corporation
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Histology Pathology and Forensic Medicine

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