ArticleCellular signalling2012
A transformation in the mechanism by which the urokinase receptor signals provides a selection advantage for estrogen receptor-expressing breast cancer cells in the absence of estrogen.
Article in Cellular signalling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Urokinase-Type Plasminogen Activator Receptor (uPAR) PET/MRI of Prostate Cancer for Noninvasive Evaluation of Aggressiveness: Comparison with Gleason Score in a Prospective Phase 2 Clinical Trial.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2021Trial
- Effects of mitotically active polyploid giant cancer cells on chemoresistance through interaction with cancer-associated fibroblasts.British journal of cancer · 2026Article
- Proteomics-Based Soluble Urokinase Plasminogen Activator Receptor Levels and Long-Term Cardiovascular Outcomes in Survivors of Breast Cancer: A UK Biobank Study.Journal of the American Heart Association · 2025Article
- Functional Validation of the Putative Oncogenic Activity ofBiomedicines · 2022Article
- Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer.Journal of translational medicine · 2022Review
- Urokinase Receptor uPAR Downregulation in Neuroblastoma Leads to Dormancy, Chemoresistance and Metastasis.Cancers · 2022Article
- uPAR PET/CT for Prognostication and Response Assessment in Patients with Metastatic Castration-Resistant Prostate Cancer Undergoing Radium-223 Therapy: A Prospective Phase II Study.Diagnostics (Basel, Switzerland) · 2021Article
- Heregulin Drives Endocrine Resistance by Altering IL-8 Expression in ER-Positive Breast Cancer.International journal of molecular sciences · 2020Article
- Targeting uPAR by CRISPR/Cas9 System Attenuates Cancer Malignancy and Multidrug Resistance.Frontiers in oncology · 2019Article
- D2A sequence of the urokinase receptor induces cell growth through αvβ3 integrin and EGFR.Cellular and molecular life sciences : CMLS · 2018Article
- The Urokinase Receptor Induces a Mesenchymal Gene Expression Signature in Glioblastoma Cells and Promotes Tumor Cell Survival in Neurospheres.Scientific reports · 2018Article
- uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy.Oncotarget · 2016Review
- Urokinase links plasminogen activation and cell adhesion by cleavage of the RGD motif in vitronectin.EMBO reports · 2016Article
- A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro.International journal of molecular medicine · 2016Article
- Src Is a Potential Therapeutic Target in Endocrine-Resistant Breast Cancer Exhibiting Low Estrogen Receptor-Mediated Transactivation.PloS one · 2016Article
- Neutralizing the EGF receptor in glioblastoma cells stimulates cell migration by activating uPAR-initiated cell signaling.Oncogene · 2015Article
- Urokinase receptor and resistance to targeted anticancer agents.Frontiers in pharmacology · 2015Review
- uPAR induces expression of transforming growth factor β and interleukin-4 in cancer cells to promote tumor-permissive conditioning of macrophages.The American journal of pathology · 2014Article
- Should EMT of Cancer Cells Be Understood as Epithelial-Myeloid Transition?Journal of Cancer · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Binding of urokinase-type plasminogen activator (uPA) to its receptor, uPAR, in estrogen receptor-α (ERα) expressing breast cancer cells, transiently activates ERK downstream of FAK, Src family kinases, and H-Ras. Herein, we show that when uPAR is over-expressed, in two separate ERα-positive breast cancer cell lines, ERK activation occurs autonomously of uPA and is sustained. Autonomous ERK activation by uPAR requires H-Ras and Rac1. A mutated form of uPAR, which does not bind vitronectin (uPAR-W32A), failed to induce autonomous ERK activation. Expression of human uPAR or mouse uPAR but not uPAR-W32A in MCF-7 cells provided a selection advantage when these cells were deprived of estrogen in cell culture for two weeks. Similarly, MCF-7 cells that express mouse uPAR formed xenografts in SCID mice that survived and increased in volume in the absence of estrogen supplementation, probably reflecting the pro-survival activity of phospho-ERK. Autonomous uPAR signaling to ERK was sensitive to the EGFR tyrosine kinase inhibitors, Erlotinib and Gefitinib. The transition in uPAR signaling from uPA-dependent and transient to autonomous and sustained is reminiscent of the transformation in ErbB2/HER2 signaling observed when this gene is amplified in breast cancer. uPAR over-expression may provide a pathway for escape of breast cancer cells from ERα-targeting therapeutics.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.