ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
Smad3 Promotes Cancer-Associated Fibroblasts Generation via Macrophage-Myofibroblast Transition.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers.
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Who cites it
144 citing papers in PubMed, 178 citations in OpenAlex.
- Progesterone and selective progesterone receptor modulator regulate tumor-associated fibroblasts in uterine leiomyomas.Genes & diseases · 2026Article
- Targeting cancer-associated fibroblasts: therapeutic strategies, translational challenges, and future perspectives.Journal of hematology & oncology · 2026Review
- Cellular crosstalk of fibroblast-myofibroblast transition in intestinal homeostasis and disease.Biomarker research · 2026Review
- Immune-stromal interactions at the crossroads of tissue injury, repair, and tumor progression.Med (New York, N.Y.) · 2026Review
- Beyond EMT: Mesenchymal drift as an emerging driver of stromal-immune reprogramming in prostate cancer.iScience · 2026Review
- Macrophage-to-myofibroblast transition-derived itaconate promotes bone metastasis in lung cancer through targeting of HSPA8.Experimental & molecular medicine · 2026Article
- Macrophage-to-Myofibroblast Transdifferentiation Contributes to Pulmonary Fibrosis via the MERTK-SPP1-SRC-TKS5 Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Convergent Microenvironment Linking Idiopathic Pulmonary Fibrosis and Lung Cancer.Expert reviews in molecular medicine · 2026Review
- Upregulation of macrophage UPP1 promotes lung adenocarcinoma metastasis through an mtROS-cGAS-NLRP3 inflammasome axis.Cell death discovery · 2026Article
- Multi-omics reveals a novel Cxcr4Clinical and translational medicine · 2026Article
- Curcumin Inhibits Renal Fibrosis by Suppressing S100A8/A9-TLR4 Signaling via Gut Microbiota-Derived Short-Chain Fatty Acid in Macrophages.Molecular nutrition & food research · 2026Article
- Macrophage Extracellular Traps in Immunity and Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Bidirectional crosstalk between cancer-associated fibroblasts and tumor immunity: shaping the microenvironment and response to immune checkpoint therapy.Experimental hematology & oncology · 2026Review
- Macrophage-derived fibronectin suppresses antitumor immunity via tissue stiffening and immunosuppressive cell induction in cancer mouse models.Nature communications · 2026Article
- Nanomaterials targeting cancer-associated fibroblasts to overcome stromal barriers in cancer immunotherapy.Journal of nanobiotechnology · 2026Review
- ASCL2-mediated macrophage-myofibroblast transition generates immunosuppressive CAF_7 in NSCLC bone metastases.Journal of experimental & clinical cancer research : CR · 2026Article
- Decoding the CAF-TAM axis: multi-omics dissection and therapeutic targeting of stromal-immune crosstalk in the tumor microenvironment.Cell death & disease · 2026Review
- Hdac11 promotes idiopathic pulmonary fibrosis through macrophage M2-type polarization and myofibroblast accumulation by inhibiting Parkin-dependent mitophagy.Nature communications · 2026Article
- Exploring and experimental validation of SLC7A11 and ferroptosis related prognostic genes in non-small cell lung cancer using bulk RNA sequencing and single-cell RNA sequencing.Biology direct · 2026Article
- PLIN3 overexpression in lung adenocarcinoma promotes M2 macrophage-myofibroblast transition in the tumor microenvironment.Biology direct · 2026Article
84 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Cancer-associated fibroblasts (CAFs) are important in tumor microenvironment (TME) driven cancer progression. However, CAFs are heterogeneous and still largely underdefined, better understanding their origins will identify new therapeutic strategies for cancer. Here, the authors discovered a new role of macrophage-myofibroblast transition (MMT) in cancer for de novo generating protumoral CAFs by resolving the transcriptome dynamics of tumor-associated macrophages (TAM) with single-cell resolution. MMT cells (MMTs) are observed in non-small-cell lung carcinoma (NSCLC) associated with CAF abundance and patient mortality. By fate-mapping study, RNA velocity, and pseudotime analysis, existence of novel macrophage-lineage-derived CAF subset in the TME of Lewis lung carcinoma (LLC) model is confirmed, which is directly transited via MMT from M2-TAM in vivo and bone-marrow-derived macrophages (BMDM) in vitro. Adoptive transfer of BMDM-derived MMTs markedly promote CAF formation in LLC-bearing mice. Mechanistically, a Smad3-centric regulatory network is upregulated in the MMTs of NSCLC, where chromatin immunoprecipitation sequencing(ChIP-seq) detects a significant enrichment of Smad3 binding on fibroblast differentiation genes in the macrophage-lineage cells in LLC-tumor. More importantly, macrophage-specific deletion and pharmaceutical inhibition of Smad3 effectively block MMT, therefore, suppressing the CAF formation and cancer progression in vivo. Thus, MMT may represent a novel therapeutic target of CAF for cancer immunotherapy.
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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.