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Cited by 67Mechanisms of cancer metastasisCancer, Hypoxia, and MetabolismMicrobial metabolism and enzyme function

Pdcd4 repression of lysyl oxidase inhibits hypoxia-induced breast cancer cell invasion

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Santhanam, A N, Baker, A R, Hegamyer, G, Kirschmann, D A, Colburn, N H·2010·Oncogene
DOI 10.1038/onc.2010.158PMC PMC3419530
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Abstract

Metastasis to bone, liver and lungs is the primary cause of death in breast cancer patients. Our studies have revealed that the novel tumor suppressor Pdcd4 inhibits breast cancer cell migration and invasion in vitro. Loss of Pdcd4 in human nonmetastatic breast cancer cells increased the expression of lysyl oxidase (LOX) mRNA. LOX is a hypoxia-inducible amine oxidase, the activity of which enhances breast cancer cell invasion in vitro and in vivo. Specific inhibition of LOX activity by beta-aminopropionitrile or small interfering RNA decreased the invasiveness of T47D and MCF7 breast cancer cells attenuated for Pdcd4 function. Most significantly, loss of Pdcd4 augments hypoxia induction of LOX as well. Conversely, overexpression of Pdcd4 significantly reversed the hypoxia induction of LOX expression in T47D cells attenuated for Pdcd4. However, Pdcd4 did not affect hypoxia-inducible factor-1 (HIF-1) protein expression or HIF-1-responsive element-luciferase activity in response to hypoxia, suggesting that Pdcd4 regulation of LOX occurs through an HIF-independent mechanism. Nevertheless, the loss of Pdcd4 early in cancer progression may have an important role in the increased sensitivity of cancer cells to hypoxia through increased LOX activity and concomitant enhanced invasiveness.

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Authors
Santhanam, A. N., Baker, A. R., Hegamyer, G., Kirschmann, D. A., & Colburn, N. H.
Affiliations
  • Frederick National Laboratory for Cancer Research (US)
  • Northwestern University (US)
Corresponding author
Santhanam, A N
Venue
Oncogene
Publisher
Springer Science and Business Media LLC
Published
2010-05-24
Volume
29
Issue
27
Pages
3921-3932
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
DOI
10.1038/onc.2010.158
PMC
PMC3419530
OpenAlex
W2065465954
Cited by
67
References
9
Citations by year
2025: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 7 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 8 · 2013: 2 · 2012: 9
FWCI
2.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (ZIABC010026)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial metabolism and enzyme function
Keywords
PDCD4, lysyl oxidase, breast cancer, tumor invasion, hypoxia, tumor suppressor, cell migration, metastasis, beta-aminopropionitrile, T47D cells, MCF-7 cells
MeSH terms
Breast Neoplasms, Cell Movement, Collagen, Drug Combinations, Humans, Laminin, Protein-Lysine 6-Oxidase, Neoplasm Invasiveness, Proteoglycans, Cell Hypoxia, Gene Expression Regulation, Neoplastic, RNA-Binding Proteins, Cell Line, Tumor, Apoptosis Regulatory Proteins, Hypoxia-Inducible Factor 1, Gene Knockdown Techniques

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