Urokinase‐type plasminogen activator up‐regulates the expression of its cellular receptor through a post‐transcriptional mechanism

Montuori, Nunzia; Mattiello, Amalia; Mancini, Alessandro; Santoli, Mariano; Taglialatela, Paola; Caputi, M; Rossi, Guido; Ragno, Pia

doi:10.1016/s0014-5793(01)03104-0

Cited by 25 publications

(28 citation statements)

References 40 publications

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“…We (28) and others (35,36) have shown that uPA induces the expression of uPAR in several cell types, including airway epithelial cells. Therefore, we hypothesized that uPA induced during sepsis enhances cell surface expression of uPAR in the lungs of LPSchallenged mice.…”

Section: Lps Enhances Upar Expression In Mouse Lung Tissue Through a mentioning

confidence: 72%

“…We have previously observed that uPA enhances uPAR expression by post-transcriptional mRNA stabilization (35,36). Therefore, we next asked if LPS-induced expression of uPAR mRNA in Beas2B cells through this mechanism.…”

Section: Effect Of Lps On Upar Mrna Stability In Beas2b Cellsmentioning

confidence: 93%

“…Previous studies indicated that post-transcriptional stabilization of uPAR mRNA involves active participation of the uPAR mRNA binding proteins, PGK and/or hnRNPC (23)(24)(25)36).…”

Section: Effect Of Lps On Pgk-upar Mrna Cdr Interactionmentioning

confidence: 99%

“…Overexpression of hnRNPC protein increases Beas2B cell surface uPAR by stabilizing uPAR mRNA expression (13). uPA induces uPAR expression through posttranscriptional stabilization of uPAR mRNA (28,36). Hence, we sought to determine if the hnRNPC-uPAR mRNA 39 UTR Figure 4.…”

Section: Effect Of Lps On the Interaction Of Pgk With Upar Mrna In Vivomentioning

confidence: 99%

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Post-Transcriptional Regulation of Urokinase-type Plasminogen Activator Receptor Expression in Lipopolysaccharide-induced Acute Lung Injury

Bhandary¹,

Velusamy²,

Shetty³

et al. 2009

Am J Respir Crit Care Med

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Rationale: Urokinase-type plasminogen activator (uPA) receptor (uPAR) is required for the recruitment of neutrophils in response to infection. uPA induces its own expression in lung epithelial cells, which involves its interaction with cell surface uPAR. Regulation of uPAR expression is therefore crucial for uPA-mediated signaling in infectious acute lung injury (ALI). Objectives: To determine the role of uPA in uPAR expression during ALI caused by sepsis. Methods: We used Western blot, Northern blot, Northwestern assay, and immunohistochemistry. Phosphate-buffered saline-and lipopolysaccharide (LPS)-treated wild-type and uPA 2/2 mice were used. Measurements and Main Results: Biological activities of uPA, including proteolysis, cell adhesion, migration, proliferation, and differentiation, are dependent on its association with uPAR. Bacterial endotoxin (LPS) is a major cause of pulmonary dysfunction and infectionassociated mortality. The present study shows that LPS induces uPAR expression both in vitro and in vivo, and that the mechanism involves post-transcriptional stabilization of uPAR mRNA by reciprocal interaction of phosphoglycerate kinase (PGK) and heterogeneous nuclear ribonucleoprotein C (hnRNPC) with uPAR mRNA coding region and 39 untranslated region determinants, respectively. The process involves tyrosine phosphorylation of PGK and hnRNPC. uPA 2/2 mice failed to induce uPAR expression after LPS treatment. In these mice, LPS treatment failed to alter the binding of PGK and hnRNPC protein with uPAR mRNA due to lack of tyrosine phosphorylation. Conclusions: Our study shows that induction of LPS-mediated uPAR expression is mediated through tyrosine phosphorylation of PGK and hnRNPC. This involves expression of uPA as an obligate intermediary.

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Section: Lps Enhances Upar Expression In Mouse Lung Tissue Through a mentioning

confidence: 72%

Section: Effect Of Lps On Upar Mrna Stability In Beas2b Cellsmentioning

confidence: 93%

“…Previous studies indicated that post-transcriptional stabilization of uPAR mRNA involves active participation of the uPAR mRNA binding proteins, PGK and/or hnRNPC (23)(24)(25)36).…”

Section: Effect Of Lps On Pgk-upar Mrna Cdr Interactionmentioning

confidence: 99%

Section: Effect Of Lps On the Interaction Of Pgk With Upar Mrna In Vivomentioning

confidence: 99%

See 2 more Smart Citations

Post-Transcriptional Regulation of Urokinase-type Plasminogen Activator Receptor Expression in Lipopolysaccharide-induced Acute Lung Injury

Bhandary¹,

Velusamy²,

Shetty³

et al. 2009

Am J Respir Crit Care Med

View full text Add to dashboard Cite

show abstract

“…26,27 Our results are in line with what is known about the ability of u -PA to up -regulate the expression of its cellular receptor at a transcriptional level, by increasing the activity of the transcriptional factor Sp1, and also at a posttranscriptional level, by promoting u -PAR mRNA stability. 28,29 The drop in u -PA would, therefore, down -regulate the expression of its receptor as detected in our experimental system. The expression of other genes, which could be related to the u -PA phenotype, such as PAI -1, t -PA, FN, and c -met (HGF receptor ), was also tested.…”

Section: Discussionmentioning

confidence: 59%

Stable expression of antisense urokinase mRNA inhibits the proliferation and invasion of human hepatocellular carcinoma cells

et al. 2003

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Urokinase -type plasminogen activator ( u -PA ) plays a key role in malignant tumor behavior. We have previously shown that the expression of high levels of u -PA mRNA in human hepatocellular carcinoma ( HCC ) biopsies was inversely correlated with the survival of the patients. In order to evaluate the involvement of u -PA in the invasive and infiltrating properties of HCC cells, the SKHep1C3 cell line was stably transfected with an expression vector containing the 5 0 portion ( 257 bp ) of u -PA cDNA in the antisense orientation. u -PA mRNA expression and its protein level and enzymatic activity were specifically inhibited in the antisense transfectants. A comparable inhibition of the u -PA receptor ( u -PAR ) mRNA and protein was also evidenced in the antisense transfected cells compared with the control ones. At the functional level, the SKHep1C3 -AS cells showed a significant reduction in proliferation, Matrigel invasion, and motility assays compared to parental and vector -alone cells. These results indicate that u -PA is an essential factor in the growth and invasiveness of human hepatocarcinoma cells. Antisense u -PA strategy might be a potential approach to reduce tumor growth as well as the invasive capacity of the malignant cells in HCC.

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Engaged urokinase receptors enhance tumor breast cell migration and invasion by upregulating αvβ5 vitronectin receptor cell surface expression

Silvestri¹,

Cattani²,

Franco

et al. 2002

Intl Journal of Cancer

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We have previously shown that urokinase receptor physically and functionally interacts with ␣v␤5 vitronectin receptor, leading to tumor breast cell migration and invasion. Here, the link between these 2 receptors was further investigated by analyzing the expression levels of urokinase receptor and ␣v␤5 integrin in 35 human breast carcinomas and 5 benign breast lesions. The occurrence of a positive correlation between urokinase receptor and ␣v␤5 protein levels in benign and malignant tumor specimens prompted us to investigate whether engaged urokinase receptors might modulate ␣v␤5 expression. Here, we report the receptor-dependent ability of catalytically inactive urokinase to upregulate the ␣v and ␤5 chains in MDA-MB-231 and MCF-7 breast carcinoma cell lines in a time-and concentration-dependent manner. This effect is dependent on protein kinase C activity and requires new protein synthesis. Accordingly, the availability of assembled ␣v␤5 receptors on the cell surface increases upon urokinase treatment, as shown by immunoprecipitation and immunocytochemical analyses. Exposure to urokinase leads to enhanced tumor cell migration and invasion, which is prevented by the "phosphorylation-like" urokinase receptor antagonist His-uPA 138E/303E , the DNA-binding drug mithramycin, the protein kinase C inhibitor calphostin C and anti-␣v␤5 antibodies. Finally, urokinase enables benign breast MCF-10A cells to cross Matrigel in a ␣v␤5-and urokinase receptor-dependent manner, indicating that urokinase controls a regulatory circuitry crucial to breast tumor progression.

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Urokinase‐type plasminogen activator up‐regulates the expression of its cellular receptor through a post‐transcriptional mechanism

Cited by 25 publications

References 40 publications

Post-Transcriptional Regulation of Urokinase-type Plasminogen Activator Receptor Expression in Lipopolysaccharide-induced Acute Lung Injury

Post-Transcriptional Regulation of Urokinase-type Plasminogen Activator Receptor Expression in Lipopolysaccharide-induced Acute Lung Injury

Stable expression of antisense urokinase mRNA inhibits the proliferation and invasion of human hepatocellular carcinoma cells

Engaged urokinase receptors enhance tumor breast cell migration and invasion by upregulating αvβ5 vitronectin receptor cell surface expression

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