ArticlePLoS genetics2022
Host CLIC4 expression in the tumor microenvironment is essential for breast cancer metastatic competence.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Article
- Chloride Intracellular Channel 2 Can Function as a Malignant Factor in Head and Neck Squamous Cell Carcinoma.Head & neck · 2026Article
- The role of KPNA3 in multiple myeloma: implications for targeting nuclear import.Apoptosis : an international journal on programmed cell death · 2026Article
- scPRINT: pre-training on 50 million cells allows robust gene network predictions.Nature communications · 2025Article
- The role of chloride intracellular channel 4 in tumors.Cancer cell international · 2025Review
- Chloride intracellular channel (CLIC) protein function in S1P-induced Rac1 activation requires membrane localization of the C-terminus, but not thiol-transferase nor ion channel activities.Frontiers in cell and developmental biology · 2025Article
- Recent advances in therapeutic use of transforming growth factor-beta inhibitors in cancer and fibrosis.Frontiers in oncology · 2025Review
- The Unique Roles of Ion Channels in Pluripotent Stem Cells in Response to Biological Stimuli.Biology · 2024Review
- Breast cancer patient-derived organoids for the investigation of patient-specific tumour evolution.Cancer cell international · 2024Article
- Chloride intracellular channels in oncology as potential novel biomarkers and personalized therapy targets: a systematic review.Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology · 2024Review
- Crosstalk between tumor and stroma modifies CLIC4 cargo in extracellular vesicles.Journal of extracellular biology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
The TGF-β-regulated Chloride Intracellular Channel 4 (CLIC4) is an essential participant in the formation of breast cancer stroma. Here, we used data available from the TCGA and METABRIC datasets to show that CLIC4 expression was higher in breast cancers from younger women and those with early-stage metastatic disease. Elevated CLIC4 predicted poor outcome in breast cancer patients and was linked to the TGF-β pathway. However, these associations did not reveal the underlying biological contribution of CLIC4 to breast cancer progression. Constitutive ablation of host Clic4 in two murine metastatic breast cancer models nearly eliminated lung metastases without reducing primary tumor weight, while tumor cells ablated of Clic4 retained metastatic capability in wildtype hosts. Thus, CLIC4 was required for host metastatic competence. Pre- and post-metastatic proteomic analysis identified circulating pro-metastatic soluble factors that differed in tumor-bearing CLIC4-deficient and wildtype hosts. Vascular abnormalities and necrosis increased in primary tumors from CLIC4-deficient hosts. Transcriptional profiles of both primary tumors and pre-metastatic lungs of tumor-bearing CLIC4-deficient hosts were consistent with a microenvironment where inflammatory pathways were elevated. Altogether, CLIC4 expression in human breast cancers may serve as a prognostic biomarker; therapeutic targeting of CLIC4 could reduce primary tumor viability and host metastatic competence.
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