ArticleOncogene2023
WNT2-SOX4 positive feedback loop promotes chemoresistance and tumorigenesis by inducing stem-cell like properties in gastric cancer.
Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- SRSF3 plays a key role in liver cancer sex disparity by facilitating hepatocyte expression of ERα and FOXA.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- RAD51AP1-MYC-Sam68 positive transcriptional feedback loop maintains lung cancer stemness.iScience · 2026Article
- Advances inOncology letters · 2026Review
- microRNA-204 as a crucial cancer stem cell related miRNA inhibits stemness of gastric cancer by targeting CD44 and EPCAM.Journal of translational medicine · 2026Article
- Targeting frizzled receptors (FZDs) for anti-tumor therapy: From orthosteric to allosteric inhibition.Acta pharmaceutica Sinica. B · 2026Review
- Exploring EZH2-Linked lncRNAs in Gastric Cancer: Insights from Sequencing Data and Gene Modulation.Biochemical genetics · 2026Article
- RhoA deficiency in chondrocyte inhibits cartilage fibrosis and ameliorates osteoarthritis progression via SOX4/MMP2 axis.Journal of orthopaedic translation · 2026Article
- MOncogene · 2026Article
- miR-96-5p antagonizes FOXQ1-driven WNT/β-catenin signaling to inhibit triple-negative breast cancer.Scientific reports · 2026Article
- The SOX4-Semaphorin3C axis promotes esophageal adenocarcinoma progression.Cancer letters · 2025Article
- Article
- SOX4 enhances tumor progression and cisplatin resistance in orthotopic mouse xenograft model of head and neck squamous cell carcinoma.BMC cancer · 2025Article
- SOX4-ZIP14-zinc metabolism mediates oncogenesis and suppresses T cell immunity in nasopharyngeal carcinoma.Cell reports. Medicine · 2025Article
- The expression of transmembrane channel-like 5 in gastric cancer and its impact on tumor progression.Scientific reports · 2025Article
- Senescent fibroblasts secrete CTHRC1 to promote cancer stemness in hepatocellular carcinoma.Cell communication and signaling : CCS · 2025Article
- mOncogene · 2025Article
- Single-cell transcriptome analysis reveals the malignant characteristics of tumour cells and the immunosuppressive landscape in HER2-positive inflammatory breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- DNA-methylation eraser TET2 activates WTIP expression to suppress an AKT-dependent chemoresistance of gastric cancer.Neoplasia (New York, N.Y.) · 2025Article
- Cancer stem cells: Bridging microenvironmental interactions and clinical therapy.Clinical and translational medicine · 2025Review
- SOX4 as a Key Oncogene Driving Tumor Invasion in Retinoblastoma.Investigative ophthalmology & visual science · 2025Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Gastric cancer (GC) is characterized by its vigorous chemoresistance to current therapies, which is attributed to the highly heterogeneous and immature phenotype of cancer stem cells (CSCs) during tumor initiation and progression. The secretory WNT2 ligand regulates multiple cancer pathways and has been demonstrated to be a potential therapeutic target for gastrointestinal tumors; however, its role involved in gastric CSCs (GCSCs) remains unclear. Here, we found that overexpression of WNT2 enhanced stemness properties to promote chemoresistance and tumorigenicity in GCSCs. Mechanistically, WNT2 was positively regulated by its transcription factor SOX4, and in turn, SOX4 was upregulated by the canonical WNT2/FZD8/β-catenin signaling pathway to form an auto-regulatory positive feedback loop, resulting in the maintenance of GCSCs self-renewal and tumorigenicity. Furthermore, simultaneous overexpression of both WNT2 and SOX4 was correlated with poor survival and reduced responsiveness to chemotherapy in clinical GC specimens. Blocking WNT2 using a specific monoclonal antibody significantly disrupted the WNT2-SOX4 positive feedback loop in GCSCs and enhanced the chemotherapeutic efficacy when synergized with the chemo-drugs 5-fluorouracil and oxaliplatin in a GCSC-derived mouse xenograft model. Overall, this study identified a novel WNT2-SOX4 positive feedback loop as a mechanism for GCSCs-induced chemo-drugs resistance and suggested that the WNT2-SOX4 axis may be a potential therapeutic target for gastric cancer treatment.
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