ArticleMolecular cancer2011
IL-17 induces AKT-dependent IL-6/JAK2/STAT3 activation and tumor progression in hepatocellular carcinoma.
Article in Molecular cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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127 citing papers in PubMed, 222 citations in OpenAlex.
- IL-17A/IL-17RA promotes invasion and activates MMP-2 and MMP-9 expression via p38 MAPK signaling pathway in non-small cell lung cancer.Molecular and cellular biochemistry · 2019Trial
- Astrocyte-derived IL-17A facilitates angiogenesis following ischemia-like injury via an IL-6-dependent STAT3-VEGF signaling cascade.Behavioral and brain functions : BBF · 2026Article
- Glycerol-mediated nose-to-brain codelivery of anti-IL-17 and anti-CD73 antibodies enhances immunotherapy for melanoma brain metastases.Science advances · 2026Article
- The Role of CD4Cells · 2026Review
- Fedratinib treatment correlates with suppressed STAT3/AKT/calpain-1 signaling and inhibits hepatocellular carcinoma progression.Translational gastroenterology and hepatology · 2026Article
- Targeting IL-17 Presents a Promising Strategy for Treating Diseases Related to the Dysregulation of Lipid Homeostasis.Mediators of inflammation · 2026Review
- Soluble cytokines and chemokines in NSCLC: drivers of immune evasion and angiogenesis.Frontiers in immunology · 2026Review
- Assessment of the main signaling pathways involved in the combined therapy of hepatocellular carcinoma using Sorafenib and NK cells in xenograft mice model.Toxicology reports · 2025Article
- Prolonged neoadjuvant hormonal therapy enhances IL-17 A/STAT3-mediated inflammation in prostate cancer.Discover oncology · 2025Article
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- Ferroptosis in Autoimmune Diseases: Research Advances and Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Prognostic Significance of HMGA1 in Hepatocellular Carcinoma: Implications for Tumor Progression and Targeted Therapy.Archives of Iranian medicine · 2025Article
- Review
- Beneficial Probiotics with New Cancer Therapies for Improved Treatment of Hepatocellular Carcinoma.Diseases (Basel, Switzerland) · 2025Review
- Targeting TM4SF1 promotes tumor senescence enhancing CD8+ T cell cytotoxic function in hepatocellular carcinoma.Clinical and molecular hepatology · 2025Article
- PLEK2 promotes migration and invasion in pancreatic ductal adenocarcinoma by MMP1 through IL-17 pathway.Molecular and cellular biochemistry · 2025Article
- Expression of interleukin-17 in oral tongue squamous cell carcinoma and its effect on biological behavior.Scientific reports · 2025Article
- Integrative bioinformatics and experimental validation unveil CRISP3 as a hypoxia-, epithelial mesenchymal transition-, and immune-related prognostic biomarker and therapeutic target in breast cancer.Frontiers in immunology · 2025Article
- Role and functional mechanisms of IL‑17/IL‑17R signaling in pancreatic cancer (Review).Oncology reports · 2024Review
- Two-sample Mendelian Randomization to evaluate the causal relationship between inflammatory arthritis and female-specific cancers.Journal of translational medicine · 2024Article
67 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe Th17 subset and IL-17 have been found in increased frequencies within certain tumors. However, their relevance in cancer biology remains controversial. This study aimed to clarify the biological action of IL-17 on hepatocellular carcinoma (HCC).
methodsEffects and underlying molecular mechanisms of IL-17 on human HCC were explored in vitro using exogenous IL-17 stimulation and in nude mice by implanting IL-17 overexpressed HCC cells. The clinical significance of IL-17 was investigated in tissue microarrays containing HCC tissues from 323 patients following hepatectomy using immunohistochemistry.
resultsAlthough exogenous IL-17 showed no direct effect on the growth rate of HCC cells in vitro, PCR and ELISA showed that IL-17 selectively augmented the secretion of diverse proinvasive factors and transwell showed a direct promotion of invasion of HCC cells by IL-17. Furthermore, transfection of IL-17 into HCC cells significantly promoted neoangiogenesis, neutrophil recruitment and tumor growth in vivo. Using siRNA mediated knockdown of AKT and STAT3, we suggested that the effects of IL-17 were operated through activation of the AKT signaling in HCC, which resulted in IL-6 production. Then, IL-6 in turn activated JAK2/STAT3 signaling and subsequently up-regulated its downstream targets IL-8, MMP2, and VEGF. Supporting these findings, in human HCC tissues, immunostaining indicated that IL-17 expression was significantly and positively associated with STAT3 phosphorylation, neutrophil infiltration and increased tumor vascularity. The clinical significance of IL-17 was authenticated by revealing that the combination of intratumoral IL-17+ cells and phospho-STAT3 served as a better prognosticator for postoperative tumor recurrence than either marker alone.
conclusionsIL-17 mediated tumor-promoting role involves a direct effect on HCC cells through IL-6/JAK2/STAT3 induction by activating the AKT pathway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.