ArticleNature communications2015
Disruption of STAT3 signalling promotes KRAS-induced lung tumorigenesis.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 149 citations in OpenAlex.
- Janus kinases restrain chronic lymphocytic leukemia cells in patients on ibrutinib: Results of a phase II trial.Cancer medicine · 2021Trial
- ERK1/2 hijack STAT3 via Thr714 phosphorylation to suppress gene expression.Cell communication and signaling : CCS · 2026Article
- Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?Journal of experimental & clinical cancer research : CR · 2025Review
- Regulatory non-coding somatic mutations as drivers of neuroblastoma.British journal of cancer · 2025Article
- Selective inhibition of canonical STAT3 signaling suppresses K-ras mutant lung tumorigenesis and reinvigorates anti-tumor immunity.Frontiers in immunology · 2025Article
- A STAT3-STING-IFN axis controls the metastatic spread of small cell lung cancer.Nature immunology · 2024Article
- The HOXC10/NOD1/ERK axis drives osteolytic bone metastasis of pan-KRAS-mutant lung cancer.Bone research · 2024Article
- Exploring Novel Frontiers: Leveraging STAT3 Signaling for Advanced Cancer Therapeutics.Cancers · 2024Review
- Stat3 Regulates Developmental Hematopoiesis and Impacts Myeloid Cell Function via Canonical and Non-Canonical Modalities.Journal of innate immunity · 2024Article
- PKCι induces differential phosphorylation of STAT3 to modify STAT3-related signaling pathways in pancreatic cancer cells.Journal of cell communication and signaling · 2023Article
- CUL4B functions as a tumor suppressor in KRAS-driven lung tumors by inhibiting the recruitment of myeloid-derived suppressor cells.Oncogene · 2023Article
- STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway.Molecular cancer · 2023Article
- JAKs and STATs from a Clinical Perspective: Loss-of-Function Mutations, Gain-of-Function Mutations, and Their Multidimensional Consequences.Journal of clinical immunology · 2023Review
- European Society of Toxicologic Pathology (Pathology 2.0 Molecular Pathology Special Interest Group): Review of In Situ Hybridization Techniques for Drug Research and Development.Toxicologic pathology · 2023Review
- Paradoxical activation of chronic lymphocytic leukemia cells by ruxolitinibFrontiers in oncology · 2023Article
- Zhoushi Qiling decoction inhibits proliferation of human prostate cancer cells through IL6/STAT3 pathway.Journal of Cancer · 2023Article
- Nanoparticle-Mediated Delivery of STAT3 Inhibitors in the Treatment of Lung Cancer.Pharmaceutics · 2022Review
- Role of STAT3 and NRF2 in Tumors: Potential Targets for Antitumor Therapy.Molecules (Basel, Switzerland) · 2022Review
- STAT3 and PD-L1 are negatively correlated with ATM and have impact on the prognosis of triple-negative breast cancer patients with low ATM expression.Breast cancer research and treatment · 2022Article
- STAT3-mediated osteogenesis and osteoclastogenesis in osteoporosis.Cell communication and signaling : CCS · 2022Review
35 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 12 institutions in 4 countries.
Funding
Abstract
STAT3 is considered to play an oncogenic role in several malignancies including lung cancer; consequently, targeting STAT3 is currently proposed as therapeutic intervention. Here we demonstrate that STAT3 plays an unexpected tumour-suppressive role in KRAS mutant lung adenocarcinoma (AC). Indeed, lung tissue-specific inactivation of Stat3 in mice results in increased Kras(G12D)-driven AC initiation and malignant progression leading to markedly reduced survival. Knockdown of STAT3 in xenografted human AC cells increases tumour growth. Clinically, low STAT3 expression levels correlate with poor survival and advanced malignancy in human lung AC patients with smoking history, which are prone to KRAS mutations. Consistently, KRAS mutant lung tumours exhibit reduced STAT3 levels. Mechanistically, we demonstrate that STAT3 controls NF-κB-induced IL-8 expression by sequestering NF-κB within the cytoplasm, thereby inhibiting IL-8-mediated myeloid tumour infiltration and tumour vascularization and hence tumour progression. These results elucidate a novel STAT3-NF-κB-IL-8 axis in KRAS mutant AC with therapeutic and prognostic relevance.
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Registered trials
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.