ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
A Selective β-Catenin-Metadherin/CEACAM1-CCL3 Axis Mediates Metastatic Heterogeneity upon Tumor-Macrophage Interaction.
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 22 papers.
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Who cites it
22 citing papers in PubMed, 24 citations in OpenAlex.
- Nested Nanowell Arrays for High-Throughput Quantitative Analysis of Cytokines from Single Macrophages.ACS nano medicine · 2026Article
- Subclonal β-catenin/YAP signaling heterogeneity accelerates ovarian cancer metastasis through a senescence-associated secretory phenotype.Cell death & disease · 2026Article
- PRC1 promotes immunosuppressive macrophages in sepsis via β-catenin/STAT3 signaling.Cellular and molecular life sciences : CMLS · 2026Article
- Trem2 activation by renal tubular debris sustains Arg1Frontiers in immunology · 2026Article
- Prognostic Significance and Immune Correlation of CCL3 Expression in Colon Adenocarcinoma: Insights From Multidatabase Analysis.Biochemistry research international · 2026Article
- Osteoblast-CD4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Development of a radiomic model to predict CEACAM1 expression and prognosis in ovarian cancer.Scientific reports · 2025Article
- HSP27/IL-6 axis promotes OSCC chemoresistance, invasion and migration by orchestrating macrophages via a positive feedback loop.Cell biology and toxicology · 2025Article
- The role of macrophage polarization in ovarian cancer: from molecular mechanism to therapeutic potentials.Frontiers in immunology · 2025Review
- Inflammatory factors collaboratively linkFrontiers in immunology · 2025Review
- Advance in therapies targeting tumor-associated macrophages in ovarian cancer.Frontiers in immunology · 2025Review
- Single-cell RNA sequencing elucidated the landscape of breast cancer brain metastases and identified ILF2 as a potential therapeutic target.Cell proliferation · 2024Article
- CCT2 prevented β-catenin proteasomal degradation to sustain cancer stem cell traits and promote tumor progression in epithelial ovarian cancer.Molecular biology reports · 2024Article
- TP63 transcriptionally regulates SLC7A5 to suppress ferroptosis in head and neck squamous cell carcinoma.Frontiers in immunology · 2024Article
- Article
- New genetic and epigenetic insights into the chemokine system: the latest discoveries aiding progression toward precision medicine.Cellular & molecular immunology · 2023Review
- The Single-Cell Landscape of Intratumoral Heterogeneity and The Immunosuppressive Microenvironment in Liver and Brain Metastases of Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- A novel stratification framework based on anoikis-related genes for predicting the prognosis in patients with osteosarcoma.Frontiers in immunology · 2023Article
- The role of carcinoembryonic antigen-related cell adhesion molecule 1 in cancer.Frontiers in immunology · 2023Review
- Immune Checkpoint and Other Receptor-Ligand Pairs Modulating Macrophages in Cancer: Present and Prospects.Cancers · 2022Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Tumor heterogeneity plays a key role in cancer relapse and metastasis, however, the distinct cellular behaviors and kinetics of interactions among different cancer cell subclones and the tumor microenvironment are poorly understood. By profiling an isogenic model that resembles spontaneous human ovarian cancer metastasis with an highly metastatic (HM) and non-metastatic (NM) tumor cell pair, one finds an upregulation of Wnt/β-catenin signaling uniquely in HM. Using humanized immunocompetent mice, one shows for the first time that activated β-catenin acts nonautonomously to modulate the immune microenvironment by enhancing infiltrating tumor-associated macrophages (TAM) at the metastatic site. Single-cell time-lapse microscopy further reveals that upon contact with macrophages, a significant subset of HM, but not NM, becomes polyploid, a phenotype pivotal for tumor aggressiveness and therapy resistance. Moreover, HM, but not NM, polarizes macrophages to a TAM phenotype. Mechanistically, β-catenin upregulates cancer cell surface metadherin, which communicates through CEACAM1 expressed on macrophages to produce CCL3. Tumor xenografts in humanized mice and clinical patient samples both corroborate the relevance of enhanced metastasis, TAM activation, and polyploidy in vivo. The results thus suggest that targeting the β-catenin-metadherin/CEACAM1-CCL3 positive feedback cascade holds great therapeutic potential to disrupt polyploidization of the cancer subclones that drive metastasis.
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Registered trials
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