ArticleCancer communications (London, England)2024
SERPINE2 promotes liver cancer metastasis by inhibiting c-Cbl-mediated EGFR ubiquitination and degradation.
Article in Cancer communications (London, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 38 citations in OpenAlex.
- CAF-derived PAI-1 serves as an EGFR ligand and fuels KRAS-mutant pancreatic cancer.Nature communications · 2026Article
- Immune, molecular and genetic profiles of gastric signet ring cell carcinoma: Recent progress and future challenges.International journal of cancer · 2026Review
- SerpinB7 promotes c-Myc-mediated glycolysis by interacting with ANXA2 to facilitate the progression of non-small cell lung cancer.Molecular cancer · 2026Article
- SERPINE2-mediated activation of JAK2/STAT3 facilitates NRF2 nuclear translocation and GCLC transcription to confer ferroptosis resistance and lenvatinib resistance in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- SIAH2-EPHB6 axis enhances filopodia formation in hepatocellular carcinoma cells by regulating RHOF.Cell & bioscience · 2026Article
- Integrated Multi-Omics Analysis Reveals Cytokine Network Dynamics and Prognostic Signatures in Hepatitis B Virus-Associated Hepatocellular Carcinoma.Applied biochemistry and biotechnology · 2026Article
- A three-protein serum risk score for predicting immunotherapy response and prognosis in non-small cell lung cancer.International journal of clinical and experimental pathology · 2026Article
- WTAP-Mediated Glutaminase Splicing Bias Suppresses Ferroptosis in Hepatocellular Carcinoma.Cancer communications (London, England) · 2026Article
- Mechanistic insights into triclosan-induced hepatotoxicity: A network toxicology and molecular docking approach.PloS one · 2026Article
- Article
- Post-Translational Modifications of Histones and Non-Histones in Liver Disease and Traditional Chinese Medicine Treatment: A Narrative Review.Pharmacogenomics and personalized medicine · 2026Review
- Navigating the Tumor Microenvironment in Colorectal Liver Metastasis: Barriers to Therapy and Emerging Opportunities.Oncology research · 2026Review
- Multi-omics insights into SERPINE2-driven post-metastatic microenvironmental reprogramming in advanced cancers: implications for molecular targeting and immunotherapy.Frontiers in immunology · 2026Review
- Integrated methylome analysis identifies an epigenetically silenced tumor suppressor RASA4 in small cell lung cancer.Communications biology · 2025Article
- TRIM24 promotes proliferation and metastasis of gastric cancer via mediating NRBP1 ubiquitination.Cell death & disease · 2025Article
- SPRY1 Interaction with CBL Promotes Vimentin Stabilization to Enhance Malignant Progression and Metastasis in Wilms Tumor.Annals of surgical oncology · 2025Article
- Comprehensive multi-omics analyses expose a precision therapy strategy that targets replication stress in hepatocellular carcinoma using WEE1 inhibition.Journal of advanced research · 2025Article
- GMPS inhibits the proliferation and migration of non-small cell lung cancer via the regulation of the DNMT 1/SERPINB2 axis.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Anti-EGFR therapy can overcome acquired resistance to the third-generation ALK-tyrosine kinase inhibitor lorlatinib mediated by activation of EGFR.Acta pharmacologica Sinica · 2025Article
- A CMTM6 Nanobody Overcomes EGFR-TKI Resistance in Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
15 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundLiver cancer is a malignancy with high morbidity and mortality rates. Serpin family E member 2 (SERPINE2) has been reported to play a key role in the metastasis of many tumors. In this study, we aimed to investigate the potential mechanism of SERPINE2 in liver cancer metastasis.
methodsThe Cancer Genome Atlas database (TCGA), including DNA methylation and transcriptome sequencing data, was utilized to identify the crucial oncogene associated with DNA methylation and cancer progression in liver cancer. Data from the TCGA and RNA sequencing for 94 pairs of liver cancer tissues were used to explore the correlation between SERPINE2 expression and clinical parameters of patients. DNA methylation sequencing was used to detect the DNA methylation levels in liver cancer tissues and cells. RNA sequencing, cytokine assays, immunoprecipitation (IP) and mass spectrometry (MS) assays, protein stability assays, and ubiquitination assays were performed to explore the regulatory mechanism of SERPINE2 in liver cancer metastasis. Patient-derived xenografts and tumor organoid models were established to determine the role of SERPINE2 in the treatment of liver cancer using sorafenib.
resultsBased on the public database screening, SERPINE2 was identified as a tumor promoter regulated by DNA methylation. SERPINE2 expression was significantly higher in liver cancer tissues and was associated with the dismal prognosis in patients with liver cancer. SERPINE2 promoted liver cancer metastasis by enhancing cell pseudopodia formation, cell adhesion, cancer-associated fibroblast activation, extracellular matrix remodeling, and angiogenesis. IP/MS assays confirmed that SERPINE2 activated epidermal growth factor receptor (EGFR) and its downstream signaling pathways by interacting with EGFR. Mechanistically, SERPINE2 inhibited EGFR ubiquitination and maintained its protein stability by competing with the E3 ubiquitin ligase, c-Cbl. Additionally, EGFR was activated in liver cancer cells after sorafenib treatment, and SERPINE2 knockdown-induced EGFR downregulation significantly enhanced the therapeutic efficacy of sorafenib against liver cancer. Furthermore, we found that SERPINE2 knockdown also had a sensitizing effect on lenvatinib treatment.
conclusionsSERPINE2 promoted liver cancer metastasis by preventing EGFR degradation via c-Cbl-mediated ubiquitination, suggesting that inhibition of the SERPINE2-EGFR axis may be a potential target for liver cancer treatment.
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