ArticleJournal of experimental & clinical cancer research : CR2022
FOXD1-dependent RalA-ANXA2-Src complex promotes CTC formation in breast cancer.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Predictive value of Slug-positive circulating tumor cells for neoadjuvant chemotherapy response in mesenchymal malignancies.Journal of cancer research and clinical oncology · 2026Observational
- Molecular subtyping and prognostic model construction based on endosome-related genes in colorectal cancer.Journal of gastrointestinal oncology · 2026Article
- CAFs-derived LAM332 promotes CTCs formation and survival via ITGA3 and contributes to the metastasis of pancreatic ductal adenocarcinoma.Cell death & disease · 2026Article
- Targeting the ANXA2-CD63-exosomal PD-L1 axis in hepatocellular carcinoma: A novel mechanism of immune evasion and its implications for precision immunotherapy.Neoplasia (New York, N.Y.) · 2026Article
- Selenium Ameliorates Aluminum Poisoning-Induced Impaired Production of Neutrophil Extracellular Traps in Chicken.Biological trace element research · 2025Article
- Machine learning-based construction of a programmed cell death-related model reveals prognosis and immune infiltration in pancreatic adenocarcinoma patients.Scientific reports · 2025Article
- Extracellular vesicles: the "Trojan Horse" within breast cancer host microenvironments.Molecular cancer · 2025Review
- Targeting ALG3/FOXD1/BNIP3 Axis Prevents Mitophagy and Gemcitabine Resistance of Nasopharyngeal Carcinoma.International journal of biological sciences · 2025Article
- Cut&tag: a powerful epigenetic tool for chromatin profiling.Epigenetics · 2024Review
- Induction of Invasive Basal Phenotype in Triple-Negative Breast Cancers by Long Noncoding RNA BORG.Cancers · 2024Article
- A Novel tsRNA, mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- FAXC interacts with ANXA2 and SRC in mitochondria and promotes tumorigenesis in cholangiocarcinoma.Cancer science · 2024Article
- Annexin A2 combined with TTK accelerates esophageal cancer progression via the Akt/mTOR signaling pathway.Cell death & disease · 2024Article
- The development and application of cleavage under targets and tagmentation (CUT&Tag) technology.Journal of biological methods · 2024Review
- Lysyl oxidase-like 4 promotes the invasiveness of triple-negative breast cancer cells by orchestrating the invasive machinery formed by annexin A2 and S100A11 on the cell surface.Frontiers in oncology · 2024Article
- Prognostic and clinicopathological significance of FOXD1 in various cancers: a meta and bioinformation analysis.Future science OA · 2024Review
- SUMOylation of RALY promotes vasculogenic mimicry in glioma cells via the FOXD1/DKK1 pathway.Cell biology and toxicology · 2023Article
- miR-30e-5p-mediated FOXD1 promotes cell proliferation by blocking cellular senescence and apoptosis through p21/CDK2/Rb signaling in head and neck carcinoma.Cell death discovery · 2023Article
- Lysine Acetylome of Breast Cancer-Derived Small Extracellular Vesicles Reveals Specific Acetylation Patterns for Metabolic Enzymes.Biomedicines · 2023Article
- Effect of various hepatectomy procedures on circulating tumor cells in postoperative patients: a case-matched comparative study.Frontiers in medicine · 2023Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundEarly metastasis is a key factor contributing to poor breast cancer (BC) prognosis. Circulating tumor cells (CTCs) are regarded as the precursor cells of metastasis, which are ultimately responsible for the main cause of death in BC. However, to date molecular mechanisms underlying CTC formation in BC have been insufficiently defined.
methodsRNA-seq was carried out in primary tissues from early-stage BC patients (with CTCs≥5 and CTCs = 0, respectively) and the validation study was conducted in untreated 80 BC patients. Multiple in vitro and in vivo models were used in functional studies. Luciferase reporter, ChIP-seq, CUT&Tag-seq, and GST-pulldown, etc. were utilized in mechanistic studies. CTCs were counted by the CanPatrol™ CTC classification system or LiquidBiospy™ microfluidic chips. ERK1/2 inhibitor SCH772984 was applied to in vivo treatment.
resultsHighly expressed FOXD1 of primary BC tissues was observed to be significantly associated with increased CTCs in BC patients, particularly in early BC patients. Overexpressing FOXD1 enhanced the migration capability of BC cells, CTC formation and BC metastasis, via facilitating epithelial-mesenchymal transition of tumor cells. Mechanistically, FOXD1 was discovered to induce RalA expression by directly bound to RalA promotor. Then, RalA formed a complex with ANXA2 and Src, promoting the interaction between ANXA2 and Src, thus increasing the phosphorylation (Tyr23) of ANXA2. Inhibiting RalA-GTP form attenuated the interaction between ANXA2 and Src. This cascade culminated in the activation of ERK1/2 signal that enhanced metastatic ability of BC cells. In addition, in vivo treatment with SCH772984, a specific inhibitor of ERK1/2, was used to dramatically inhibit the CTC formation and BC metastasis.
conclusionHere, we report a FOXD1-dependent RalA-ANXA2-Src complex that promotes CTC formation via activating ERK1/2 signal in BC. FOXD1 may serve as a prognostic factor in evaluation of BC metastasis risks. This signaling cascade is druggable and effective for overcoming CTC formation from the early stages of BC.
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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.