Tenascin-C signaling through induction of 14-3-3 tau

Doris Martin1, Marianne Brown-Luedi, Ruth Chiquet-Ehrismann

  • 1Friedrich Miescher Institute, Novartis Forschungsstiftung, CH-4002 Basel, Switzerland.

Insights

Tenascin-C influences tumor cell growth by increasing 14-3-3 tau expression. This adaptor protein enhances tumor cell adhesion and proliferation on tenascin-C, impacting mammary carcinoma cell behavior.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Oncology

Background:

  • Cellular behavior and gene expression differ based on extracellular matrix components.
  • Tenascin-C and fibronectin are key matrix proteins influencing cell adhesion and morphology.
  • 14-3-3 proteins are crucial phospho-serine/threonine-binding adaptors involved in various cellular processes.

Purpose of the Study:

  • To identify differentially expressed transcripts in MCF-7 cells cultured on tenascin-C versus fibronectin.
  • To investigate the role of elevated 14-3-3 tau in tenascin-C-mediated tumor cell responses.
  • To determine the impact of 14-3-3 tau on tumor cell adhesion, morphology, and growth on tenascin-C.

Main Methods:

  • cDNA subtraction screening to identify differentially expressed genes.
  • MCF-7 cell culture on tenascin-C and fibronectin substrates.
  • Transfection of MCF-7, HT1080, and T98G cells with 14-3-3 tau.
  • Analysis of cell morphology, F-actin staining, adhesion, survival, and growth rates.

Main Results:

  • Cells grown on tenascin-C exhibited irregular shapes, while those on fibronectin were flat.
  • Elevated levels of 14-3-3 tau transcripts and protein were observed in cells on tenascin-C.
  • Overexpression of 14-3-3 tau in MCF-7 cells resulted in flattened morphology on tenascin-C and increased growth rate.
  • 14-3-3 tau-expressing HT1080 and T98G cells adhered and survived on tenascin-C, unlike parental cells.

Conclusions:

  • Tenascin-C promotes tumor cell growth, potentially through increased 14-3-3 tau expression.
  • 14-3-3 tau enhances tumor cell adhesion and growth on tenascin-C.
  • This interaction suggests a mechanism by which tenascin-C supports tumor progression.

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