Evidence map›Paper›PMID 17657740›Full record

ArticleInternational journal of cancer2007

RNAi-mediated downregulation of urokinase plasminogen activator receptor and matrix metalloprotease-9 in human breast cancer cells results in decreased tumor invasion, angiogenesis and growth.

Sateesh Kunigal, Sajani S Lakka, Christopher S Gondi, Norman Estes, Jasti S Rao

RetractedOpen access · bronzeAbstract readRetracted Publication
In one paragraph

Article in International journal of cancer, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 85 citations in OpenAlex.

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4 · The record

Corrections and comments

  • Retraction · 2021-02-26Duplication of/in Image · Manipulation of Images · Original Data and/or Images not Provided and/or not Available · Unreliable Results and/or Conclusions · · see also: https://pubpeer.com/publications/B688FD0E2CA8FAC16DDD2C226D4A17
  • Retracted
5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Sateesh KunigalDepartment of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA.
Sajani S Lakka
Christopher S Gondi
Norman Estes
Jasti S Rao
Illinois College · USUniversity of Illinois Urbana-Champaign · US

Funding

Cath B and uPAR si RNA constructs regressed glioma growthR01CA116708 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI O'BRYAN, JOHN P · 2005 to 2014
$2.9M
Inhibition of glioma tumor growth by antisense MMP-9R01NS047699 · NINDS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI RAO, JASTI S. · 2003 to 2011
$2.5M
Role of uPA and uPAR in Human Glioma InvasivenessR01CA075557 · NCI · UNIVERSITY OF TEXAS MD ANDERSON CAN CTR · PI RAO, JASTI S. · 1998 to 2009
$2.3M
Growth inhibition of brain tumors by cord blood stem cellsR01NS057529 · NINDS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI RAO, JASTI S. · 2006 to 2010
$1.8M
Role of TFPI-2 in human gliomas invasivenessR01CA095058 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI RAO, JASTI S. · 2003 to 2007
$1.5M
Suppression of glioma invasion by a bicistronic constuctR01CA092393 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI RAO, JASTI S. · 2003 to 2007
$1.4M
NCI NIH HHS CA 116708NCI NIH HHS CA 75557NCI NIH HHS CA 92393NCI NIH HHS CA 95058NCI NIH HHS R01 CA075557NCI NIH HHS R01 CA092393NCI NIH HHS R01 CA095058NCI NIH HHS R01 CA116708NINDS NIH HHS NS47699NINDS NIH HHS NS57529NINDS NIH HHS R01 NS047699NINDS NIH HHS R01 NS057529
6 · The paper itself

Abstract

The serine protease urokinase-type plasminogen activator (uPA) plays a significant role in tumor cell invasion and metastasis when bound to its specific receptor, uPAR (also known as CD87). In addition to the uPA-uPAR system, matrix metalloproteinases (MMPs) are involved in tumor cell invasion and metastasis. In this study, we achieved specific inhibition of uPAR and MMP-9 using RNAi technology. We introduced small interfering RNA to downregulate the expression of uPAR and MMP-9 (pUM) in breast cancer cell lines (MDA MB 231 and ZR 75 1). In vitro angiogenesis studies indicated a decrease in the angiogenic potential of the treated cells; in particular, a remarkable decrease was observed in the cells treated with bicistronic construct (pUM) in comparision to the controls. Additionally, bicistronic construct inhibited the formation of capillary-like structures in in vivo models of angiogenesis. Similarly, the invasive potential and migration decreased dramatically when treated with the bicistronic construct as shown by matrigel invasion and migration assays. These results suggest a synergistic effect from the simultaneous downregulation of uPAR and MMP-9. We also assessed the levels of phosphorylated forms of MAPK, ERK and AKT signaling pathway molecules and found reduction in the levels of these molecules in cells treated with the bicistronic construct as compared to the control cells. Furthermore, targeting both uPAR and MMP-9 totally regressed orthotopic breast tumors in nude mice. In conclusion, our results provide evidence that the simultaneous downregulation of uPAR and MMP-9 using RNAi technology may provide an effective tool for breast cancer therapy.

Indexed as

Down-RegulationAnimalsBreast NeoplasmsCell Line, TumorCell ProliferationEnzyme ActivationGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHumansMatrix Metalloproteinase 9MiceMice, NudeMitogen-Activated Protein KinasesNeoplasm InvasivenessPhosphorylationProto-Oncogene Proteins c-aktMatrix Metalloproteinase 9Mitogen-Activated Protein KinasesPLAUR protein, humanPlaur protein, mouseProto-Oncogene Proteins c-aktReceptors, Cell SurfaceReceptors, Urokinase Plasminogen ActivatorRNA, Small Interfering

Identifiers

PMID17657740
PMCPMC2396459
OpenAlexW2003170155

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.