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

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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

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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…

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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: Yang, H-S
Asangani, I
Post, S
Allgayer, H
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: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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

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

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