ArticleCell reports2016
STAT3 and STAT6 Signaling Pathways Synergize to Promote Cathepsin Secretion from Macrophages via IRE1α Activation.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
112 citing papers in PubMed, 200 citations in OpenAlex.
- Multi-level transcriptional control of specific macrophage responses.The EMBO journal · 2026Review
- CD36: bridging metabolism, inflammation, and reproduction.npj metabolic health and disease · 2026Review
- Extracellular matrix and proteolysis: mechanisms driving irreversible changes and shaping cell behavior.The FEBS journal · 2026Review
- Enterococcus faecalis and lipoteichoic acid up-regulated PD-L1 of macrophage through TLR and IRE1 α/XBP1 signaling axis.Odontology · 2026Article
- The Lysosome-Cathepsin Axis in Pancreatic Cancer: Mechanisms of Stromal Remodeling, Immune Evasion, and Therapy Resistance.Biomolecules · 2026Review
- Endoplasmic reticulum stress in antitumor immunity and immunotherapy resistance: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Probing the activity of cysteine cathepsins in inflammatory bowel diseases.Scientific reports · 2025Article
- Targeting the unfolded protein response for cancer therapy: mitigating tumor adaptation and immune suppression.Biomarker research · 2025Review
- Mechanistic insights into IL-6-mediated NK cell dysfunction in NSCLC via the IRE1α-XBP1s-STAT3-UBE2S axis.NPJ precision oncology · 2025Article
- Gasdermin C cleavage by Cathepsin S modulates Rab7 vesicles in intestinal epithelial cells to amplify anti-helminth immunity.Immunity · 2025Article
- Coxiella burnetii manipulates the lysosomal protease cathepsin B to facilitate intracellular success.Nature communications · 2025Article
- Cathepsin B promotes optic nerve axonal regeneration.Neuroreport · 2025Article
- Review
- Endoplasmic Reticulum Stress: Triggers Microenvironmental Regulation and Drives Tumor Evolution.Cancer medicine · 2025Review
- Article
- Genomics-Driven Immunotherapy: Advancing Cancer Treatment through Personalized Approaches.Current genomics · 2025Review
- Endoplasmic Reticulum Stress in Cancer Progression: A Comprehensive Review of Its Role and Mechanisms.International journal of medical sciences · 2025Review
- CaFBBA advances · 2025Article
- Targeting of TAMs: can we be more clever than cancer cells?Cellular & molecular immunology · 2024Review
- Influencing immunity: role of extracellular vesicles in tumor immune checkpoint dynamics.Experimental & molecular medicine · 2024Review
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Tumor-associated macrophages play critical roles during tumor progression by promoting angiogenesis, cancer cell proliferation, invasion, and metastasis. Cysteine cathepsin proteases, produced by macrophages and cancer cells, modulate these processes, but it remains unclear how these typically lysosomal enzymes are regulated and secreted within the tumor microenvironment. Here, we identify a STAT3 and STAT6 synergy that potently upregulates cathepsin secretion by macrophages via engagement of an unfolded protein response (UPR) pathway. Whole-genome expression analyses revealed that the TH2 cytokine interleukin (IL)-4 synergizes with IL-6 or IL-10 to activate UPR via STAT6 and STAT3. Pharmacological inhibition of the UPR sensor IRE1α blocks cathepsin secretion and blunts macrophage-mediated cancer cell invasion. Similarly, genetic deletion of STAT3 and STAT6 signaling components impairs tumor development and invasion in vivo. Together, these findings demonstrate that cytokine-activated STAT3 and STAT6 cooperate in macrophages to promote a secretory phenotype that enhances tumor progression in a cathepsin-dependent manner.
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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.