ArticleCarcinogenesis2012
CLIC4 is a tumor suppressor for cutaneous squamous cell cancer.
Article in Carcinogenesis, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage.Nature communications · 2021Pooled it
- The role of chloride intracellular channel 4 in tumors.Cancer cell international · 2025Review
- RNA-binding protein DND1 participates in migration, invasion, and EMT of prostate cancer cells by degrading CLIC4.Histology and histopathology · 2024Article
- CLIC4 Function in the Epithelial-Mesenchymal Transition of Epithelial Odontogenic Lesions.Head and neck pathology · 2024Article
- Crosstalk between tumor and stroma modifies CLIC4 cargo in extracellular vesicles.Journal of extracellular biology · 2023Article
- The stromal immunoexpression of CLIC4 may be related to the difference in the biological behavior between oral squamous cell carcinoma and oral verrucous carcinoma.Medicina oral, patologia oral y cirugia bucal · 2023Article
- Nuclear localisation sequences of chloride intracellular channels 1 and 4 facilitate nuclear import via interactions with import mediator importin-α: An empirical and theoretical perspective.Journal of molecular recognition : JMR · 2023Article
- Structure-based discovery and in vitro validation of inhibitors of chloride intracellular channel 4 protein.Computational and structural biotechnology journal · 2023Article
- Host CLIC4 expression in the tumor microenvironment is essential for breast cancer metastatic competence.PLoS genetics · 2022Article
- N6-methyladenosine demethylase FTO suppressed prostate cancer progression by maintaining CLIC4 mRNA stability.Cell death discovery · 2022Article
- Circular RNA_0033596 aggravates endothelial cell injury induced by oxidized low-density lipoprotein via microRNA-217-5p /chloride intracellular channel 4 axis.Bioengineered · 2022Article
- DNA Hypermethylation Involves in the Down-Regulation of Chloride Intracellular Channel 4 (CLIC4) Induced by Photodynamic Therapy.Biomedicines · 2021Article
- Membrane Transporters and Channels in Melanoma.Reviews of physiology, biochemistry and pharmacology · 2021Review
- CLIC4 and CLIC1 bridge plasma membrane and cortical actin network for a successful cytokinesis.Life science alliance · 2020Article
- The Unusual Suspects in Cytokinesis: Fitting the Pieces Together.Frontiers in cell and developmental biology · 2020Review
- Intracellular Chloride Channels: Novel Biomarkers in Diseases.Frontiers in physiology · 2020Review
- Article
- CLIC1 and CLIC4 complement CA125 as a diagnostic biomarker panel for all subtypes of epithelial ovarian cancer.Scientific reports · 2018Article
- A G-Quadruplex Structure in the Promoter Region ofInternational journal of molecular sciences · 2018Article
- Three Decades of Chloride Intracellular Channel Proteins: From Organelle to Organ Physiology.Current protocols in pharmacology · 2018Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Chloride intracellular channel (CLIC) 4 is a member of a redox-regulated, metamorphic multifunctional protein family, first characterized as intracellular chloride channels. Current knowledge indicates that CLICs participate in signaling, cytoskeleton integrity and differentiation functions of multiple tissues. In metabolically stressed skin keratinocytes, cytoplasmic CLIC4 is S-nitrosylated and translocates to the nucleus where it enhances transforming growth factor-β (TGF-β) signaling by protecting phospho-Smad 2 and 3 from dephosphorylation. CLIC4 expression is diminished in multiple human epithelial cancers, and the protein is excluded from the nucleus. We now show that CLIC4 expression is reduced in chemically induced mouse skin papillomas, mouse and human squamous carcinomas and squamous cancer cell lines, and the protein is excluded from the nucleus. The extent of reduction in CLIC4 coincides with progression of squamous tumors from benign to malignant. Inhibiting antioxidant defense in tumor cells increases S-nitrosylation and nuclear translocation of CLIC4. Adenoviral-mediated reconstitution of nuclear CLIC4 in squamous cancer cells enhances TGF-β-dependent transcriptional activity and inhibits growth. Adenoviral targeting of CLIC4 to the nucleus of tumor cells in orthografts inhibits tumor growth, whereas elevation of CLIC4 in transgenic epidermis reduces de novo chemically induced skin tumor formation. In parallel, overexpression of exogenous CLIC4 in squamous tumor orthografts suppresses tumor growth and enhances TGF-β signaling. These results indicate that CLIC4 suppresses the growth of squamous cancers, that reduced CLIC4 expression and nuclear residence detected in cancer cells is associated with the altered redox state of tumor cells and the absence of detectable nuclear CLIC4 in cancers contributes to TGF-β resistance and enhances tumor development.
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Registered trials
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.