ArticleOncogenesis2017
Growth-induced stress enhances epithelial-mesenchymal transition induced by IL-6 in clear cell renal cell carcinoma via the Akt/GSK-3β/β-catenin signaling pathway.
Article in Oncogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 101 citations in OpenAlex.
- Intracellular complement Factor H promotes tumor progression through modulation of cell cycle and actin cytoskeleton.Communications biology · 2026Article
- Metabolic starvation-induced cell swelling drives solid stress in tumors.bioRxiv : the preprint server for biology · 2026Article
- Diversity of Effects of Mechanical Influences on Living Systems and Aqueous Solutions.International journal of molecular sciences · 2025Review
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- Focus on mechano-immunology: new direction in cancer treatment.International journal of surgery (London, England) · 2025Review
- Research progress on mechanisms of tumor immune microenvironment and gastrointestinal resistance to immunotherapy: mini review.Frontiers in immunology · 2025Review
- Solid stress compression enhances breast cancer cell migration through the upregulation of Interleukin-6.Frontiers in cell and developmental biology · 2025Article
- The mechanopathology of the tumor microenvironment: detection techniques, molecular mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2025Review
- Compressive stresses in cancer: characterization and implications for tumour progression and treatment.Nature reviews. Cancer · 2024Review
- Mechanical models and measurement methods of solid stress in tumors.Applied microbiology and biotechnology · 2024Review
- Toward innovative approaches for exploring the mechanically regulated tumor-immune microenvironment.APL bioengineering · 2024Review
- Epithelial-Mesenchymal Transition: A Fundamental Cellular and Microenvironmental Process in Benign and Malignant Prostate Pathologies.Biomedicines · 2024Review
- The role of stromal cells in epithelial-mesenchymal plasticity and its therapeutic potential.Discover oncology · 2024Review
- NOP16 promotes hepatocellular carcinoma progression and triggers EMT through the Keap1-Nrf2 signaling pathway.Technology and health care : official journal of the European Society for Engineering and Medicine · 2024Article
- Comprehensive analysis of skin growth-related hub genes and microenvironment characterization in a mouse expanded skin model.Frontiers in immunology · 2024Article
- Biophysics in tumor growth and progression: from single mechano-sensitive molecules to mechanomedicine.Oncogene · 2023Review
- Proactive and reactive roles of TGF-β in cancer.Seminars in cancer biology · 2023Review
- Sonomechanobiology: Vibrational stimulation of cells and its therapeutic implications.Biophysics reviews · 2023Review
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Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stromal cell populations in the tumor microenvironment (TME) play a critical role in the oncogenesis and metastasis of renal cell carcinoma. In this study, we found that there are α-smooth muscle actin positive (α-SMA (+)) cells in the stroma of clear cell renal cell carcinoma (ccRCC) tissues, and their numbers are significantly associated with poor survival in ccRCC patients. Interleukin 6 (IL-6) is a critical diver that induces α-SMA (+) cells in ccRCC tissues via promotion of epithelial to mesenchymal transition (EMT) and stimulates migration and invasion in ccRCC. Peritumoral CD4+ T cells are the main source of IL-6 in ccRCC tissues. In addition to biochemical factors, mechanical compression within tumors affects tumor cell behavior. Tumors grown in a confined space exhibit intratumoral compressive stress and, with sufficient pressure, stress-stimulated migration of cancer cells. Moreover, a combination of IL-6 secreted by CD4+ T cells and growth-induced solid stress further contributes to the regulation of cancer cell morphogenesis, EMT and acquisition of a stemness phenotype. The effects in the combination group were driven by the Akt/GSK-3β/β-catenin signaling pathway, and deregulation of β-catenin expression was predictive of poor outcome in ccRCC patients. Notably, the expression of a cancer stem cell marker, CD44, was correlated with T stage, high Fuhrman grade and metastasis in ccRCC. These data provide evidence for new stress-reducing and IL-6 targeting strategies in cancer therapy.
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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.