ArticleCell death discovery2022
A positive feedback loop: RAD18-YAP-TGF-β between triple-negative breast cancer and macrophages regulates cancer stemness and progression.
Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed.
- Hippo pathway at the crossroads of stemness and therapeutic resistance in breast cancer.Molecular oncology · 2026Review
- Targeted delivery of TGF-β inhibitor via LHRH-NanoTi reverses the NAT10/ac4C-mediated cisplatin-induced immunosuppressive tumor microenvironment in ovarian cancer.Journal of nanobiotechnology · 2026Article
- Progress for RAD18's mechanism in breast cancer radioresistant.Open life sciences · 2026Review
- Cell competition within breast tumor microenvironment: emerging role of cancer stem cells and immune cells in tumor progression and therapeutic implications.Frontiers in oncology · 2026Review
- Macrophage regulation of tumor cell dormancy and the dormant niche: an overview in solid tumors.Cancer metastasis reviews · 2025Review
- Reprogramming the breast tumor immune microenvironment: cold-to-hot transition for enhanced immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Targeting the Hippo Pathway in Breast Cancer: A Proteomic Analysis of Yes-Associated Protein Inhibition.International journal of molecular sciences · 2025Article
- Unraveling the triad of hypoxia, cancer cell stemness, and drug resistance.Journal of hematology & oncology · 2025Review
- HSP27/IL-6 axis promotes OSCC chemoresistance, invasion and migration by orchestrating macrophages via a positive feedback loop.Cell biology and toxicology · 2025Article
- Hippo/YAP signaling's multifaceted crosstalk in cancer.Frontiers in cell and developmental biology · 2025Review
- Inflammation-associated drug resistance and tumor growth in TNBC.Frontiers in immunology · 2025Review
- Unveiling the contribution of tumor-associated macrophages in driving epithelial-mesenchymal transition: a review of mechanisms and therapeutic Strategies.Frontiers in pharmacology · 2024Review
- Implications of ubiquitination and the maintenance of replication fork stability in cancer therapy.Bioscience reports · 2023Review
- Blockade of TGF-β signalling alleviates human adipose stem cell senescence induced by native ECM in obesity visceral white adipose tissue.Stem cell research & therapy · 2023Article
- Article
- Mannose-Coated Reconstituted Lipoprotein Nanoparticles for the Targeting of Tumor-Associated Macrophages: Optimization, Characterization, and In Vitro Evaluation of Effectiveness.Pharmaceutics · 2023Article
- Betulinic Acid Inhibits the Stemness of Gastric Cancer Cells by Regulating the GRP78-TGF-β1 Signaling Pathway and Macrophage Polarization.Molecules (Basel, Switzerland) · 2023Article
- Targeting cancer stem cell plasticity in triple-negative breast cancer.Exploration of targeted anti-tumor therapy · 2023Review
- Signaling pathways governing the maintenance of breast cancer stem cells and their therapeutic implications.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a key regulator of the DNA translesion synthesis (TLS) pathway, RAD18 is error-prone and contributes to the accumulation of DNA mutations. Our previous study showed that it plays an essential role in the progression of multiple tumors. However, the mechanism through which RAD18 influences triple-negative breast cancer (TNBC), especially the interaction between tumor cells and the tumor microenvironment, remains elusive. In this study, we showed that RAD18 expression is markedly higher in patients with high T stage TNBC and inversely correlated with prognosis. High expression of RAD18 facilitated a highly stem-cell phenotype through the Hippo/YAP pathway, which supports the proliferation of TNBC. In addition, the cytokine byproduct TGF-β activates macrophages to have an M2-like tumor-associated macrophage (TAM) phenotype. Reciprocally, TGF-β from TAMs activated RAD18 in TNBC to enhance tumor stemness, forming a positive feedback loop. Inhibition of YAP or TGF-β breaks this loop and suppresses cancer stemness and proliferation In nude mice, RAD18 promoted subcutaneous transplanted tumor growth and M2-type TAM recruitment. Collectively, the RAD18-YAP-TGF-β loop is essential for the promotion of the stemness phenotype by TNBC and could be a potential therapeutic target for TNBC.
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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.