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The interaction of interleukin-8 and PTEN inactivation promotes the malignant progression of head and neck squamous cell carcinoma via the STAT3 pathway
Open accessAbstract
Interleukin-8 (IL-8) expression correlates with poor prognosis in many cancers, including head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism is poorly understood. In this study, we found that overexpression of IL-8 correlated with poor outcome in HNSCC patients. IL-8 significantly increased cellular proliferation, migration, and invasion ability both in vitro and in vivo, which could be blocked by a CXCR1/2 inhibitor. IL-8 promoted the expression of MMP2, MMP9, snail, and vimentin in HNSCC cells. Furthermore, IL-8 could inactivate PTEN via phosphorylation, and then inactivated PTEN affected the phosphorylation of STAT3. Recombinant PTEN that internalized in cytoplasm decreased the expression of phosphorylated STAT3, while knockdown of PTEN led to the increased expression of phosphorylated STAT3. A STAT3 inhibitor could reverse the upregulation of invasion-associated proteins mediated by IL-8 stimulation. Furthermore, overexpression of snail and inactivated PTEN jointly promoted the autocrine effect of IL-8 on tumor cells. Last, there were positive correlations between IL-8 and snail, vimentin expression in HNSCC tissues. In summary, our study demonstrates that PTEN acts as a novel “molecular switch” to regulate IL-8/STAT3 signaling, promoting the progression of HNSCC, and indicating that this pathway may be a potential therapeutic target for HNSCC.
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IL-8 and MMP9 may affect the activity of cells critical to bone healing and may influence the bone healing process.
“IL-8 and MMP9 may affect the activity of these cells, which are critical participating cells in the bone healing process, in the manner described above and may, therefore, influence the bone healing process”
From Modulation of fracture healing by senescence-associated secretory phenotype (SASP): a narrative review of the current literature (2024) · cites this paper as [100]
The Results section on IL-8 and CXCR1/2 reports that IL-8 increased migration and proliferation in head and neck cancer cells and increased MMP9 expression (page unavailable). It does not show that MMP9 itself affects cell activity, or that either molecule affects cells involved in bone healing or the bone-healing process. The paper’s “wound healing assay” measures cancer-cell migration, not bone repair. (LLM, conf=0.82)
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Metadata
- Authors
- Xu, Q., Ma, H., Chang, H., Feng, Z., Zhang, C., & Yang, X.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Capital Medical University (CN)
- Corresponding author
- Ma, Hailong
- Zhang, Chenping
- Yang, Xi
- Venue
- Cell Death & Disease
- Published
- 2020-05-29
- Volume
- 11
- Issue
- 5
- Pages
- 405-405
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC7260373
- OpenAlex
- W3029472285
- Cited by
- 50
- References
- 39
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 7 · 2023: 11 · 2022: 8 · 2021: 8
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Death and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81902747, 81602367)
- Science and Technology Commission of Shanghai Municipality (YDZX20173100004422)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- interleukin-8, PTEN inactivation, head and neck squamous cell carcinoma, STAT3 signaling, tumor progression, CXCR1/2, MMP-2, MMP-9, snails, vimentin, epithelial-mesenchymal transition, tumor invasion, autocrine signaling, therapeutic target
- MeSH terms
- Snail Family Transcription Factors, Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms, Humans, Phosphorylation, Prognosis, Vimentin, Signal Transduction, Up-Regulation, Gene Expression Regulation, Neoplastic, Interleukin-8, Disease Progression, Receptors, Interleukin-8A, Receptors, Interleukin-8B, Cell Line, Tumor, STAT3 Transcription Factor, PTEN Phosphohydrolase
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.
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