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Trop-2 inhibits prostate cancer cell adhesion to fibronectin through the β1 integrin-RACK1 axis

Marco Trerotola1, Jing Li, Saverio Alberti

  • 1Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Journal of Cellular Physiology
|March 2, 2012
PubMed

Insights

Trop-2, a protein found in prostate cancer (PrCa), regulates cell adhesion to fibronectin by activating the β(1) integrin-RACK1-FAK-Src pathway, impacting cancer aggressiveness.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Trop-2 is a transmembrane glycoprotein often overexpressed in human carcinomas, including prostate cancer (PrCa).
  • While Trop-2's role in cell-cell adhesion is suggested by homology to Trop-1/EpCAM and binding to tight junction proteins, its function in extracellular matrix adhesion is unexplored.
  • PrCa aggressiveness is a critical factor in patient outcomes.

Purpose of the Study:

  • To investigate the role of Trop-2 in prostate cancer cell adhesion to the extracellular matrix.
  • To elucidate the molecular mechanisms by which Trop-2 influences cell adhesion and signaling pathways.

Main Methods:

  • Trop-2 expression was manipulated using shRNA-mediated silencing and ectopic expression in PrCa cell lines.
  • Cell adhesion assays were performed using fibronectin (FN) as the extracellular matrix ligand.
  • Western blotting and co-immunoprecipitation were used to analyze protein interactions and signaling pathway activation (β(1) integrins, RACK1, Src, FAK, IGF-IR).

Main Results:

  • Trop-2 expression in PrCa cells correlates with increased cancer aggressiveness.
  • Trop-2 expression inhibits PrCa cell adhesion to fibronectin, independent of α(v) β(5) integrin.
  • Trop-2 enhances the association of β(1) integrins with RACK1, promoting RACK1's translocation to the cell membrane.
  • Trop-2 activates Src and FAK signaling pathways via the β(1) integrin-RACK1 interaction, without involving IGF-IR.

Conclusions:

  • Trop-2 acts as a novel regulator of prostate cancer cell adhesion to fibronectin.
  • The mechanism involves the activation of the β(1) integrin-RACK1-FAK-Src signaling axis.
  • Trop-2's role in modulating cell adhesion and signaling pathways contributes to prostate cancer aggressiveness.

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