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Originally published as MBC in Press, 10.1091/mbc.E07-05-0496 on August 8, 2007

Vol. 18, Issue 10, 4003-4012, October 2007

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The Synovial Sarcoma SYT-SSX2 Oncogene Remodels the Cytoskeleton through Activation of the Ephrin PathwayFormula

Roy Barco*, Laura B. Hunt*, Andrea L. Frump*, Christina B. Garcia*, Andrew Benesh*, Robert L. Caldwell{dagger}, and Josiane E. Eid*

*Department of Cancer Biology and {dagger}Vanderbilt Orthopedic Institute, Vanderbilt University Medical Center, Nashville, TN 37232

Submitted May 25, 2007; Revised July 9, 2007; Accepted July 26, 2007
Monitoring Editor: Mark Ginsberg

Synovial sarcoma is a soft tissue cancer associated with a recurrent t(X:18) translocation that generates one of two fusion proteins, SYT-SSX1 or SYT-SSX2. In this study, we demonstrate that SYT-SSX2 is a unique oncogene. Rather than confer enhanced proliferation on its target cells, SYT-SSX2 instead causes a profound alteration of their architecture. This aberrant morphology included elongation of the cell body and formation of neurite-like extensions. We also observed that cells transduced with SYT-SSX2 often repulsed one another. Notably, cell repulsion is a known component of ephrin signaling. Further analysis of SYT-SSX2–infected cells revealed significant increases in the expression and activation of Eph/ephrin pathway components. On blockade of EphB2 signaling SYT-SSX2 infectants demonstrated significant reversion of the aberrant cytoskeletal phenotype. In addition, we discovered, in parallel, that SYT-SSX2 induced stabilization of the microtubule network accompanied by accumulation of detyrosinated Glu tubulin and nocodazole resistance. Glu tubulin regulation was independent of ephrin signaling. The clinical relevance of these studies was confirmed by abundant expression of both EphB2 and Glu tubulin in SYT-SSX2–positive synovial sarcoma tissues. These results indicate that SYT-SSX2 exerts part of its oncogenic effect by altering cytoskeletal architecture in an Eph-dependent manner and cytoskeletal stability through a concurrent and distinct pathway.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-05-0496) on August 8, 2007.

Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Josiane E. Eid (josiane.eid{at}vanderbilt.edu)




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 Sci SignalHome page
M. Lackmann and A. W. Boyd
Eph, a Protein Family Coming of Age: More Confusion, Insight, or Complexity?
Sci. Signal., April 15, 2008; 1(15): re2 - re2.
[Abstract] [Full Text] [PDF]


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