Transcriptional regulation of the urokinase receptor (u-PAR)--a central molecule of invasion and metastasis

Biol Chem. 2003 May;384(5):755-61. doi: 10.1515/BC.2003.084.

Abstract

The phenomenon of tumor-associated proteolysis has been acknowledged as a decisive step in the progression of cancer. This short review focuses on the urokinase receptor (u-PAR), a central molecule involved in tumor-associated invasion and metastasis, and summarizes the transcriptional regulation of u-PAR. The urokinase receptor (u-PAR) is a heavily glycosylated cell surface protein and binds the serine protease urokinase specifically and with high affinity. It consists of three similar cysteine-rich repeats and is anchored to the cell membrane via a GPI-anchor. The u-PAR gene comprises 7 exons and is located on chromosome 19q13. Transcriptional activation of the u-PAR promoter region can be induced by binding of transcription factors (Sp1, AP-1, AP-2, NF-kappa B). One current study gives an example for transcriptional downregulation of u-PAR through a PEA3/ets transcriptional silencing element. Knowledge of the molecular regulation of this molecule in tumor cells could be very important for diagnosis and therapy in the near future.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Down-Regulation
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Promoter Regions, Genetic / genetics
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Urokinase Plasminogen Activator
  • Regulatory Sequences, Nucleic Acid
  • Transcription Factors / metabolism
  • Transcriptional Activation / physiology*

Substances

  • PLAUR protein, human
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Transcription Factors