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A novel oncogenic pathway by TLS-CHOP involving repression of MDA-7/IL-24 expression

K Oikawa1, M Tanaka, S Itoh

  • 1Department of Molecular Pathology, Tokyo Medical University, Shinjuku-ku, Japan.

British Journal of Cancer
|May 17, 2012
PubMed
Abstract

Insights

Translocated in liposarcoma-CCAAT/enhancer binding protein homologous protein (TLS-CHOP) is crucial for myxoid liposarcoma growth by repressing the anticancer cytokine MDA-7/IL-24. Targeting TLS-CHOP offers a promising therapeutic strategy for MLS.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • The chimeric oncoprotein TLS-CHOP (FUS-DDIT3) is prevalent in human myxoid liposarcoma (MLS).
  • The precise molecular function of TLS-CHOP in MLS pathogenesis is not well understood.

Purpose of the Study:

  • To elucidate the molecular role of TLS-CHOP in MLS development.
  • To investigate the relationship between TLS-CHOP and the anticancer cytokine MDA-7/IL-24.

Main Methods:

  • Utilized small interfering RNA (siRNA) to knockdown TLS-CHOP expression in MLS-derived cell lines.
  • Analyzed global gene expression profiles using microarray technology.

Main Results:

  • Knockdown of TLS-CHOP significantly inhibited MLS cell proliferation.
  • TLS-CHOP knockdown led to the induction of melanoma differentiation-associated gene 7 (MDA-7)/interleukin-24 (IL-24) expression.
  • Simultaneous knockdown of both TLS-CHOP and MDA-7/IL-24 did not impede MLS cell growth, suggesting MDA-7/IL-24's role in TLS-CHOP's function.

Conclusions:

  • Repression of MDA-7/IL-24 expression by TLS-CHOP is essential for MLS tumor growth.
  • TLS-CHOP emerges as a potential therapeutic target for the treatment of myxoid liposarcoma.

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