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The SYT-SSX fusion protein down-regulates the cell proliferation regulator COM1 in t(x;18) synovial sarcoma

Michiko Ishida1, Mamiko Miyamoto, Sayu Naitoh

  • 1Genter for Medical Genomics, Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji Chuo-ku, Tokyo 104-0045, Japan.

Molecular and Cellular Biology
|November 15, 2006
PubMed

Insights

Synovial sarcoma development involves SYT-SSX fusion proteins. Researchers found this fusion down-regulates COM1, a cell proliferation regulator, suggesting COM1 restoration could be a therapeutic strategy for synovial sarcoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Chromosomal translocations, particularly in soft-tissue sarcomas, generate fusion proteins critical for tumorigenesis.
  • Synovial sarcoma is characterized by the t(X;18)(p11.2;q11.2) translocation, creating SYT-SSX fusion proteins.
  • The precise downstream targets and functions of SYT-SSX fusion proteins remain largely unelucidated.

Purpose of the Study:

  • To investigate the functional consequences of SYT-SSX fusion proteins in synovial sarcoma development.
  • To identify downstream targets regulated by the SYT-SSX fusion protein.
  • To evaluate the therapeutic potential of restoring COM1 expression in synovial sarcoma.

Main Methods:

  • Analysis of SYT-SSX fusion protein's effect on SYT transcriptional coactivator function.
  • Gene expression profiling using oligonucleotide microarrays in SYT-SSX1-expressing HeLa cells.
  • Assessment of COM1 expression levels in synovial sarcoma tissues and cell lines.
  • Investigation of conditional COM1 expression's impact on synovial sarcoma cell proliferation and apoptosis.

Main Results:

  • SYT-SSX fusion protein exhibits dominant-negative function against SYT.
  • SYT-SSX1 directly down-regulates the expression of COM1, a cell proliferation regulator.
  • COM1 is expressed at low levels in synovial sarcoma.
  • Restoring COM1 expression induces apoptosis and reduces cell growth and colony formation in synovial sarcoma cells.

Conclusions:

  • SYT-SSX fusion protein dysregulates COM1 expression, contributing to synovial sarcoma pathogenesis.
  • COM1 acts as a tumor suppressor in synovial sarcoma.
  • Restoration of COM1 expression represents a potential therapeutic strategy for synovial sarcoma.

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