ArticleMolecular cancer2014
Human epididymis protein 4 in association with Annexin II promotes invasion and metastasis of ovarian cancer cells.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- Serum HE4 and polymorphisms in MMP9 and MMP13 associated with survival outcome in patients with endometrial carcinoma: a retrospective cohort study and nomogram development.Future science OA · 2026Article
- Evaluation of cerebrospinal fluid human epididymis protein 4 for leptomeningeal metastasis in non-small cell lung cancer: a prospective cohort study.BMC cancer · 2026Article
- Integrative Single-Cell and Bulk Transcriptomic Profiling Reveals Ferroptosis-Driven Heterogeneity of Ovarian Cancer Epithelial Cells.International journal of women's health · 2026Article
- Investigating the potential causal link between BPA and ovarian carcinogenesis: a network toxicology and mendelian randomization study on the CTRC/PRDX1/SKP1 pathway.Journal of ovarian research · 2025Article
- Human epididymis protein 4-annexin II binding promotes aberrant epithelial-fibroblast crosstalk in pulmonary fibrosis.Communications biology · 2025Article
- Spatial and single-cell transcriptomics reveal cellular heterogeneity and a novel cancer-promoting Treg cell subset in human clear-cell renal cell carcinoma.Journal for immunotherapy of cancer · 2025Article
- Article
- Development and validation of an ultrasound‑based radiomics nomogram to predict lymph node status in patients with high-grade serous ovarian cancer: a retrospective analysis.Journal of ovarian research · 2024Article
- Integrated multiomics characterization reveals cuproptosis-related hub genes for predicting the prognosis and clinical efficacy of ovarian cancer.Frontiers in immunology · 2024Article
- WFDC3 inhibits tumor metastasis by promoting the ERβ-mediated transcriptional repression of TGFBR1 in colorectal cancer.Cell death & disease · 2023Article
- Preoperative prediction of miliary changes in the small bowel mesentery in advanced high-grade serous ovarian cancer using MRI radiomics nomogram.Abdominal radiology (New York) · 2023Article
- Human Epididymis Protein 4 and Lewis y Enhance Chemotherapeutic Resistance in Epithelial Ovarian Cancer Through the p38 MAPK Pathway.Advances in therapy · 2022Article
- The Role of Human Epididymis Protein 4 in the Diagnosis and Prognosis of Diseases: An Umbrella Review of Systematic Reviews and Meta-Analyses of Observational Studies.Frontiers in medicine · 2022Review
- Exosomal ANXA2 derived from ovarian cancer cells regulates epithelial-mesenchymal plasticity of human peritoneal mesothelial cells.Journal of cellular and molecular medicine · 2021Article
- Human epididymis protein 4 promotes P‑glycoprotein‑mediated chemoresistance in ovarian cancer cells through interactions with Annexin II.Molecular medicine reports · 2021Article
- YWHAE as an HE4 interacting protein can influence the malignant behaviour of ovarian cancer by regulating the PI3K/AKT and MAPK pathways.Cancer cell international · 2021Article
- MicroRNAs as the critical regulators of cisplatin resistance in gastric tumor cells.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021Review
- Identification of Pan-Cancer Biomarkers Based on the Gene Expression Profiles of Cancer Cell Lines.Frontiers in cell and developmental biology · 2021Article
- Interaction of CD147 and human epididymis protein 4 promotes invasion and metastasis of ovarian cancer.Journal of Cancer · 2021Article
- WFDC Protein: A Promising Diagnosis Biomarker of Ovarian Cancer.Journal of Cancer · 2021Review
Corrections and comments
- Retracted
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe objective of the present study was to identify human epididymis protein 4 (HE4) interacting proteins and explore the mechanisms underlying their effect on ovarian cancer cell invasion and metastasis.
methodsHE4 interacting proteins were identified by mass spectrometry and validated by co-immunoprecipitation and pull-down assays. The scratch test, the Transwell assay and animal experiments were used to assess the invasive and metastatic abilities of ovarian cancer cells before and after transfection and HE4 protein treatment. HE4 and annexin II protein expression in epithelial ovarian tissues was detected by immunohistochemistry, and the relation between their expression levels was examined.
resultsAnnexin II was identified as an HE4 interacting protein. HE4 and annexin II binding interaction promoted ovarian cancer cell invasion and metastasis. HE4 and annexin II expression levels were significantly higher in malignant epithelial ovarian tissues than in benign and normal epithelial ovarian tissues, and they were higher in tissues with lymph node metastases than in those without. HE4 gene interference downregulated the expression of MAPK and the FOCAL adhesion signaling pathway-associated molecules MKNK2 and LAMB2, and HE4 protein supplementation reversed this effect.
conclusionThe binding interaction between HE4 and annexin II activates the MAPK and FOCAL adhesion signaling pathways, promoting ovarian cancer cell invasion and metastasis.
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Registered trials
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