ArticleMolecular and cellular biology2016
Cystatin E/M Suppresses Tumor Cell Growth through Cytoplasmic Retention of NF-κB.
Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- The Landscape of Disulfidptosis in Preeclampsia Reveals a Novel 5-Gene Diagnostic Signature via Machine Learning.International journal of women's health · 2026Article
- Research on the role and mechanisms of Cystatin 6 in disease pathosis and development.Frontiers in molecular biosciences · 2026Review
- Cystatin 6 (CST6) and Legumain (LGMN) are potential mediators in the pathogenesis of preeclampsia.Scientific reports · 2025Article
- Enhanced CTLA-4 blockade anti-tumor immunity with APG-157 combination in a murine head and neck cancer.Cancer medicine · 2024Article
- Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail.Cancer research communications · 2024Article
- Type 2 Cystatins and Their Roles in the Regulation of Human Immune Response and Cancer Progression.Cancers · 2023Review
- Cytokines profile in neonatal and adult wild-type mice post-injection of U. S. pediatric vaccination schedule.Brain, behavior, & immunity - health · 2021Article
- Review
- CST6 protein and peptides inhibit breast cancer bone metastasis by suppressing CTSB activity and osteoclastogenesis.Theranostics · 2021Article
- Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer.The Journal of biological chemistry · 2020Article
- Identification of lncRNA-associated differential subnetworks in oesophageal squamous cell carcinoma by differential co-expression analysis.Journal of cellular and molecular medicine · 2020Article
- Up-regulated CST5 inhibits bone resorption and activation of osteoclasts in rat models of osteoporosis via suppression of the NF-κB pathway.Journal of cellular and molecular medicine · 2019Article
- Investigation of the clinical significance and prospective molecular mechanisms of cystatin genes in patients with hepatitis B virus‑related hepatocellular carcinoma.Oncology reports · 2019Article
- Proteomic Profiling of Primary Human Acute Myeloid Leukemia Cells Does Not Reflect Their Constitutive Release of Soluble Mediators.Proteomes · 2018Article
- An Immunosuppressive Tick Salivary Gland Protein DsCystatin Interferes With Toll-Like Receptor Signaling by Downregulating TRAF6.Frontiers in immunology · 2018Article
- Synergistic Activity with NOTCH Inhibition and Androgen Ablation in ERG-Positive Prostate Cancer Cells.Molecular cancer research : MCR · 2017Article
- Cystatin C deficiency suppresses tumor growth in a breast cancer model through decreased proliferation of tumor cells.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We and others have shown that the cystatin E/M gene is inactivated in primary human tumors, pointing to its role as a tumor suppressor gene. However, the molecular mechanism of tumor suppression is not yet understood. Using plasmid-directed cystatin E/M gene overexpression, a lentivirus-mediated tetracycline-inducible vector system, and human papillomavirus 16 (HPV 16) E6 and E7 gene-immortalized normal human epidermal keratinocytes, we demonstrated intracellular and non-cell-autonomous apoptotic growth inhibition of tumor cell lines and that growth inhibition is associated with cytoplasmic retention of NF-κB. We further demonstrated decreased phosphorylation of IκB kinase (IKKβ) and IκBα in the presence of tumor necrosis factor alpha (TNF-α), confirming the role of cystatin E/M in the regulation of the NF-κB signaling pathway. Growth suppression of nude mouse xenograft tumors carrying a tetracycline-inducible vector system was observed with the addition of doxycycline in drinking water, confirming that the cystatin E/M gene is a tumor suppressor gene. Finally, immunohistochemical analyses of cervical carcinoma in situ and primary tumors have shown a statistically significant inverse relationship between the expression of cystatin E/M and cathepsin L and a direct relationship between the loss of cystatin E/M expression and nuclear expression of NF-κB. We therefore propose that the cystatin E/M suppressor gene plays an important role in the regulation of NF-κB.
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