Role of urokinase receptor in tumor progression and development

Hyangsoon Noh, Sungguan Hong, Shuang Huang

Research output: Contribution to journalReview article

75 Citations (Scopus)

Abstract

Elevated level of urokinase receptor (uPAR) is detected in various aggressive cancer types and is closely associated with poor prognosis of cancers. Binding of uPA to uPAR triggers the conversion of plasminogen to plasmin and the subsequent activation of metalloproteinases. These events confer tumor cells with the capability to degrade the components of the surrounding extracellular matrix, thus contributing to tumor cell invasion and metastasis. uPA-uPAR interaction also elicits signals that stimulate cell proliferation/survival and the expression of tumor-promoting genes, thus assisting tumor development. In addition to its interaction with uPA, uPAR also interacts with vitronectin and this interaction promotes cancer metastasis by activating Rac and stimulating cell migration. Although underlying mechanisms are yet to be fully elucidated, uPAR has been shown to facilitate epithelial-mesenchymal transition (EMT) and induce cancer stem cell-like properties in breast cancer cells. The fact that uPAR lacks intracellular domain suggests that its signaling must be mediated through its co-receptors. Indeed, uPAR interacts with diverse transmembrane proteins including integrins, ENDO180, G protein-coupled receptors and growth factor receptors in cancer cells and these interactions are proven to be critical for the role of uPAR in tumorigenesis. Inhibitory peptide that prevents uPA-uPAR interaction has shown the promise to prolong patients' survival in the early stage of clinical trial. The importance of uPAR's co-receptor in uPAR's tumor- promoting effects implicate that anti-cancer therapeutic agents may also be developed by disrupting the interactions between uPAR and its functional partners.

Original languageEnglish (US)
Pages (from-to)487-495
Number of pages9
JournalTheranostics
Volume3
Issue number7
DOIs
StatePublished - Sep 3 2013

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Urokinase-Type Plasminogen Activator
Neoplasms
Neoplasm Metastasis
Vitronectin
Epithelial-Mesenchymal Transition
Growth Factor Receptors
Neoplastic Stem Cells
Plasminogen
Fibrinolysin
Metalloproteases
G-Protein-Coupled Receptors
Integrins
Cell Communication
Cell Movement
Extracellular Matrix
Cell Survival
Carcinogenesis
Cell Proliferation
Clinical Trials
Breast Neoplasms

Keywords

  • Urokinase receptor
  • uPA
  • uPAR

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Cite this

Role of urokinase receptor in tumor progression and development. / Noh, Hyangsoon; Hong, Sungguan; Huang, Shuang.

In: Theranostics, Vol. 3, No. 7, 03.09.2013, p. 487-495.

Research output: Contribution to journalReview article

Noh, Hyangsoon ; Hong, Sungguan ; Huang, Shuang. / Role of urokinase receptor in tumor progression and development. In: Theranostics. 2013 ; Vol. 3, No. 7. pp. 487-495.
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