STAT3 is required but not sufficient for EGF receptor-mediated migration and invasion of human prostate carcinoma cell lines
Open accessAbstract
Growth factor-induced migration is a rate-limiting step in tumour invasiveness. The molecules that regulate this cellular behaviour would represent novel targets for limiting tumour cell progression. Epidermal growth factor (EGF) receptor (EGFR)-mediated motility, present in both autocrine and paracrine modes in prostate carcinomas, requires de novo transcription to persist over times greater than a few hours. Therefore, we sought to define specific signalling pathways that directly alter cellular transcription. Signal transducer and activator of transcription 3 (STAT3) is activated, as determined by electrophoretic motility shift assays, by EGFR in DU145 and PC3 human prostate carcinoma cells in addition to the motility model NR6 fibroblast cell line. Inhibition of STAT3 activity by antisense or siRNA downregulation or expression of a dominant-negative construct limited cell motility as determined by an in vitro wound healing assay and invasiveness through a extracellular matrix barrier. The expression of constitutively activated STAT3 did not increase the migration, which indicates that STAT3 is necessary but not sufficient for EGFR-mediated migration. These findings suggest that STAT3 signalling may be a new target for limiting prostate tumour cell invasion. In a microarray gene analysis of what transcription units are altered by EGF in a STAT3-dependent manner we found that the expression of motility-limiting VASP protein and the apoptosis nexus caspase 3 were both downregulated upon EGF exposure. These findings suggest a molecular basis for the STAT3 dependence of EGFR-mediated prostate tumour progression.
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STAT3 is necessary for EGFR-mediated migration and invasion in prostate carcinoma cells.
“Similarly, STAT3 is necessary for EGFR-mediated migration and invasion in prostate carcinoma cells.85”
From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [85]
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Critical analysis of the potential for targeting STAT3 in human malignancy
Grandis, J., & Peyser (2013) · OncoTargets and Therapy · doi:10.2147/ott.s47903 · Cited by 24 · see citing works
“Similarly, STAT3 is necessary for EGFR-mediated migration and invasion in prostate carcinoma cells.(85) In addition, shRNA knockdown of STAT3 in Tu-2449 glioma cells leads to decreased PDPN expression and microvilli formation relative to vector-infected cells.”
Self-citation
- Authors
- Zhou, W., Grandis, J. R., & Wells, A.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Wells, A
- Venue
- British Journal of Cancer
- Published
- 2006-06-27
- Volume
- 95
- Issue
- 2
- Pages
- 164-171
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2360627
- OpenAlex
- W2146889623
- Cited by
- 47
- References
- 1
- Citations by year
- 2024: 1 · 2020: 2 · 2017: 4 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 4 · 2012: 2
- FWCI
- 2.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- STAT3, epidermal growth factor receptor, prostate cancer, cell migration, tumor invasion, transcriptional regulation, VASP, caspase-3, siRNA knockdown, antisense inhibition, wound healing assay, tumor progression
- MeSH terms
- Vasodilator-Stimulated Phosphoprotein, Cell Movement, Extracellular Matrix, Fibroblasts, Humans, Male, Microfilament Proteins, Neoplasm Invasiveness, Phosphoproteins, Prostatic Neoplasms, Immunoblotting, Signal Transduction, Cell Adhesion Molecules, Apoptosis, Disease Progression, Caspases, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, RNA, Small Interfering, Cell Line, Tumor, STAT3 Transcription Factor, Caspase 3, ErbB Receptors, In Vitro Techniques
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