CoChat
Sign Up
Cited by 163Protease and Inhibitor MechanismsMechanisms of cancer metastasisTGF-β signaling in diseases

Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors

Leupold, J H, Yang, H-S, Colburn, N H, Asangani, I, Post, S, Allgayer, H·2007·Oncogene
DOI 10.1038/sj.onc.1210234
Open this paper in CoChat — free account

Abstract

Tumor suppressor Pdcd4 has recently been shown to inhibit invasion by activating activator protein-1 (AP-1); however, little is known of the functionally significant Pdcd4-target genes. The urokinase receptor (u-PAR) promotes invasion/metastasis, and is associated with poor cancer-patient survival. The present study was conducted (1) to investigate a role for Pdcd4 in intravasation, invasion and u-PAR regulation, and (2) to describe mechanisms by which this is achieved. Fourteen cell lines showed reciprocal expression of u-PAR/Pdcd4. Resected tumor/normal tissues of 29 colorectal cancer patients demonstrated a significant inverse correlation between Pdcd4/u-PAR. siRNA-Pdcd4-transfected GEO cells significantly increased endogenous u-PAR mRNA/protein. A u-PAR-promoter-chloramphenicol acetyl transferase (CAT)-reporter was reduced in activity with increasing Pdcd4 expression in RKO. Deletion of a putative Sp-1-binding site (-402/-350) inhibited u-PAR promoter regulation by Pdcd4, this being paralleled by a reduction of Sp1 binding to this region in pdcd4-transfected cells. Pdcd4-transfected cells showed an increase in Sp3 binding to u-PAR promoter region -152/-135, the deletion of which reduces the ability of Pdcd4 to suppress u-PAR promoter activity. Surprisingly, the u-PAR-AP-1 site was not targeted by Pdcd4. Finally, RKO cells overexpressing Pdcd4 showed an inhibition of invasion/intravasation (chicken embryo metastasis assay). These data suggest Pdcd4 as a new negative regula…

Integrity signals

Registry

Crossref · 10.1038/sj.onc.1210234

Cites

63 of 63 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • PDCD4 interacts with Sp1 and Sp3 inhibiting u-PAR expression and tumor invasion/intravasion.

    “It was shown that PDCD4 interacts with Sp1 and Sp3 inhibiting the u-PAR expression and tumor invasion/intravasion [39].”

    From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [39]

  • The anti-tumor activity of PDCD4 is well documented in in vitro systems, especially by using colon cancer cell lines.

    “The anti-tumor activity of PDCD4 is well documented in invitro systems especially by using colon cancer cell lines [24,39]”

    From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [39]

Cites

Flagged first, then by citations

1 of the 64 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Leupold, J. H., Yang, H.-S., Colburn, N. H., Asangani, I., Post, S., & Allgayer, H.
Affiliations
  • German Cancer Research Center (DE)
  • National Institutes of Health (US)
  • Heidelberg University (DE)
Corresponding author
Allgayer, H
ORCID
Venue
Oncogene
Publisher
Springer Science and Business Media LLC
Published
2007-02-12
Volume
26
Issue
31
Pages
4550-4562
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
DOI
10.1038/sj.onc.1210234
OpenAlex
W2038623184
Cited by
163
References
64
Citations by year
2026: 3 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 7 · 2017: 8 · 2016: 13 · 2015: 8 · 2014: 18 · 2013: 15 · 2012: 11
FWCI
4.25
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
PDCD4, tumor suppressor, urokinase receptor, Sp1, Sp3, transcriptional regulation, tumor invasion, intravasation, colorectal cancer, metastasis, activator protein-1
MeSH terms
Binding Sites, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Receptors, Cell Surface, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Sp1 Transcription Factor, RNA-Binding Proteins, Disease Progression, Tumor Suppressor Proteins, Cell Line, Tumor, Apoptosis Regulatory Proteins, Sp Transcription Factors, Sp3 Transcription Factor, Receptors, Urokinase Plasminogen Activator

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review