Expression of angiogenic regulators, VEGF and leptin, is regulated by the EGF/PI3K/STAT3 pathway in colorectal cancer cells
Open accessAbstract
Both leptin and vascular endothelial growth factor (VEGF) are growth and angiogenic cytokines that are upregulated in different types of cancer and have been implicated in neoplastic progression. Here we investigated the molecular mechanism by which leptin and VEGF expression are regulated in colon cancer by epidermal growth factor (EGF). In colon cancer cell line HT‐29, EGF induced the binding of signal transducer and activator transcription 3 (STAT3) to STAT3 consensus motifs within the VEGF and leptin promoters and stimulated leptin and VEGF mRNA and protein synthesis. All these EGF effects were significantly blocked when HT‐29 cells were treated with an inhibitor of the phosphoinositide 3‐kinase (PI3K) pathway, LY294002, or with small interfering RNA (siRNA) targeting STAT3. Thus, our study identified the EGF/PI3K/STAT3 signaling as an essential pathway regulating VEGF and leptin expression in EGF‐responsive colon cancer cells. This suggests that STAT3 pathways might constitute attractive pharmaceutical targets in colon cancer patients where anti‐EGF receptor drugs are ineffective. J. Cell. Physiol. 221: 189–194, 2009. © 2009 Wiley‐Liss, Inc
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STAT3 is a critical regulator of the tumor microenvironment.
“STAT3 is a critical regulator of the tumor microenvironment.”
From Critical analysis of the potential for targeting STAT3 in human malignancy (2013) · cites this paper as [87]
The Abstract and Discussion (page not available) show that STAT3 regulates expression of the angiogenic factors VEGF and leptin in EGF-stimulated colorectal cancer cells. That supports a role in one aspect of the tumor microenvironment, but the paper does not establish the broader claim that STAT3 is a critical regulator of the tumor microenvironment as a whole. (LLM, conf=0.82)
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- Authors
- Cascio, S., Ferla, R., D'Andrea, A., Gerbino, A., Bazan, V., Surmacz, E., & Russo, A.
- Affiliations
- University of Palermo (IT)
- Temple University (US)
- Corresponding author
- Russo, Antonio
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2009-06-02
- Volume
- 221
- Issue
- 1
- Pages
- 189-194
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- OpenAlex
- W2146696632
- Cited by
- 53
- References
- 43
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 8 · 2013: 6 · 2012: 4
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- vascular endothelial growth factor, leptin, epidermal growth factor, PI3K signaling, STAT3, colorectal cancer, angiogenesis, gene expression regulation, promoter binding, LY294002, anti-EGFR therapy resistance, therapeutic target
- MeSH terms
- Cell Nucleus, Epidermal Growth Factor, Humans, Promoter Regions, Genetic, Protein Binding, RNA, Messenger, Colorectal Neoplasms, Up-Regulation, Gene Expression Regulation, Neoplastic, Neovascularization, Physiologic, HT29 Cells, Phosphatidylinositol 3-Kinases, Leptin, Gene Silencing, Vascular Endothelial Growth Factor A, STAT3 Transcription Factor
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 ›
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