ArticleOncotarget2016
Lung cancer-derived galectin-1 contributes to cancer associated fibroblast-mediated cancer progression and immune suppression through TDO2/kynurenine axis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 158 citations in OpenAlex.
- In vivo inhibition of TDO2 in fibroids results in widespread alteration in the tumor transcriptome.Clinical science (London, England : 1979) · 2026Article
- Radiation-Induced Alterations in Cancer-Associated Fibroblasts: Drivers of Tumor Radioresistance and Therapeutic Targets.Biomolecules · 2026Review
- High-Penetrance Rare Variants Underlying Familial Lung Cancer Risk: Insights From Genetic Epidemiology of Lung Cancer Consortium.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Metabolic crosstalk among cancer-associated fibroblasts, adipocytes and immune cells as an immunosuppressive tumor microenvironment driver.Experimental & molecular medicine · 2026Review
- Spatially resolved tryptophan-kynurenine niches in HNSCC: immunometabolic microdomains and therapeutic implications.Frontiers in immunology · 2026Review
- A tryptophan metabolism-related gene signature predicts prognosis and immune features in cutaneous melanoma.Frontiers in immunology · 2026Article
- Galectins at the crossroads of tumor immunity, metabolism, and metastasis: mechanisms, therapeutic resistance, and translational opportunities.Frontiers in immunology · 2026Review
- Depletion of tryptophanyl-tRNA synthetase and tryptophan accumulation triggers p53-dependent apoptosis.Cell death discovery · 2025Article
- Immune-oncology-microbiome axis in lung cancer: from carcinogenesis to therapy-a narrative review.Translational lung cancer research · 2025Review
- FAPNature communications · 2025Article
- Tryptophan metabolism: From physiological functions to key roles and therapeutic targets in cancer (Review).Oncology reports · 2025Review
- Overcoming cancer treatment resistance: Unraveling the role of cancer-associated fibroblasts.Journal of the National Cancer Center · 2025Review
- Cancer-Associated Fibroblasts as the "Architect" of the Lung Cancer Immune Microenvironment: Multidimensional Roles and Synergistic Regulation with Radiotherapy.International journal of molecular sciences · 2025Review
- Cancer‑associated fibroblasts: a pivotal regulator of tumor microenvironment in the context of radiotherapy.Cell communication and signaling : CCS · 2025Review
- Review
- The Kynurenine Pathway and Indole Pathway in Tryptophan Metabolism Influence Tumor Progression.Cancer medicine · 2025Review
- TDO2 + cancer-associated fibroblasts mediate cutaneous squamous cell carcinoma immune escape via impeding infiltration of CD8 + T cells.Cancer immunology, immunotherapy : CII · 2025Article
- Promotion Mechanisms of Stromal Cell-Mediated Lung Cancer Development Within Tumor Microenvironment.Cancer management and research · 2025Review
- A comprehensive analysis of the tryptophan metabolism-related gene signature to predict the prognosis of esophageal squamous cell carcinoma based on multi-omics.Frontiers in molecular biosciences · 2025Article
- Fibroblast activation protein and the tumour microenvironment: challenges and therapeutic opportunities.Oncology reviews · 2025Review
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Communication between cancer cells and their microenvironment plays an important role in cancer development, but the precise mechanisms by which cancer-associated fibroblasts (CAF) impact anti-cancer immunity and cancer progression in lung cancer are poorly understood. Here, we report that lung fibroblasts when activated by lung cancer cells produce tryptophan metabolite kynurenine (Kyn) that inhibits dendritic cells' differentiation and induces cancer growth as well as migration. We identified TDO2 (tryptophan 2,3-dioxygenase) as the main enzyme expressed in fibroblasts capable of tryptophan metabolism. Mechanistically, condition medium of CAF or exogenous kynurenine stimulated AKT, with no lysine 1 (WNK1) and cAMP response element-bindingprotein (CREB) phosphorylation in lung cancer cells. Inhibition of the AKT/CREB pathway prevents cancer proliferation, while inhibition of the AKT/ WNK1 reverted epithelial-to-mesenchymal transition and cancer migration induced by kynurenine. Moreover, we also demonstrate that lung cancer-derived galectin-1 contributes to the upregulation of TDO2 in CAF through an AKT-dependent pathway. Immunohistochemical analysis of lung cancer surgical specimens revealed increased TDO2 expression in the fibroblasts adjacent to the cancer. Furthermore, in vivo studies showed that administration of TDO2 inhibitor significantly improves DCs function and T cell response, and decreases tumor metastasis in mice. Taken together, our data identify the feedback loop, consisting of cancer-derived galectin-1 and CAF-producing kynurenine, that sustains lung cancer progression. These findings suggest that targeting this pathway may be a promising therapeutic strategy.
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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.