ArticleThe Journal of clinical investigation2021
CLIC1 recruits PIP5K1A/C to induce cell-matrix adhesions for tumor metastasis.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 73 citations in OpenAlex.
- Review
- A cryptic-site ligand stabilizes a non-canonical interface and blocks membrane insertion of the chloride intracellular channel CLIC1.The Journal of biological chemistry · 2026Article
- KANK2 at focal adhesions regulates their maintenance and dynamics, while at fibrillar adhesions it influences cell migration via microtubule-dependent mechanism.Cell communication and signaling : CCS · 2026Article
- Targeting PIP5K ameliorates hepatic cancer by inhibiting PI3K/AKT and the autophagy mechanism and enhancing ROS-mediated apoptosis.Frontiers in pharmacology · 2026Article
- PIP5K-Ras bistability triggers plasma membrane symmetry breaking to define cellular polarity and regulate migration.bioRxiv : the preprint server for biology · 2025Article
- The CLIC1-PKM2 axis orchestrates glycolytic metabolism to accelerate gastric cancer progression.Journal of translational medicine · 2025Article
- The chloride intracellular channel 1 (CLIC1) is essential for microglial morphodynamics and neuroinflammation.Science advances · 2025Article
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
- KLHL23 and RhoGDI coordinate CDC42 inactivation ensuring membrane homeostasis.Nature chemical biology · 2025Article
- The function of chloride channels in digestive system disease (Review).International journal of molecular medicine · 2025Review
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- CLIC1 Supports Mechanisms Related to Platelet Activation and Thrombosis.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Article
- Enhancing HepG2 cell apoptosis with a combined nanoparticle delivery of miR-128-3p agomir and Oroxin B: A novel drug delivery approach based on PI3K-AKT and VEGF pathway crosstalk.Asian journal of pharmaceutical sciences · 2025Article
- Intratumoral microbiota, fatty acid metabolism, and tumor microenvironment constitute an unresolved trinity in colon adenocarcinoma.Scientific reports · 2025Article
- Exosomes: their role and therapeutic potential in overcoming drug resistance of gastrointestinal cancers.Frontiers in oncology · 2025Review
- Chloride Intracellular Channel 1 Enhances Glioblastoma Cell Migration and Epithelial-Mesenchymal Transition by Activating the ERK1/2 Signaling Pathway.Current protein & peptide science · 2025Article
- Pathophysiological role of ion channels and transporters in hepatocellular carcinoma.Cancer gene therapy · 2024Review
- Multi-stage mechanisms of tumor metastasis and therapeutic strategies.Signal transduction and targeted therapy · 2024Review
- Integrating Machine Learning and Mendelian Randomization Determined a Functional Neurotrophin-Related Gene Signature in Patients with Lower-Grade Glioma.Molecular biotechnology · 2024Article
- Targeting RORγ inhibits the growth and metastasis of hepatocellular carcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Membrane protrusion and adhesion to the extracellular matrix, which involves the extension of actin filaments and formation of adhesion complexes, are the fundamental processes for cell migration, tumor invasion, and metastasis. How cancer cells efficiently coordinate these processes remains unclear. Here, we showed that membrane-targeted chloride intracellular channel 1 (CLIC1) spatiotemporally regulates the formation of cell-matrix adhesions and membrane protrusions through the recruitment of PIP5Ks to the plasma membrane. Comparative proteomics identified CLIC1 upregulated in human hepatocellular carcinoma (HCC) and associated with tumor invasiveness, metastasis, and poor prognosis. In response to migration-related stimuli, CLIC1 recruited PIP5K1A and PIP5K1C from the cytoplasm to the leading edge of the plasma membrane, where PIP5Ks generate a phosphatidylinositol 4,5-bisphosphate-rich (PIP2-rich) microdomain to induce the formation of integrin-mediated cell-matrix adhesions and the signaling for cytoskeleon extension. CLIC1 silencing inhibited the attachment of tumor cells to culture plates and the adherence and extravasation in the lung alveoli, resulting in suppressed lung metastasis in mice. This study reveals what we believe is an unrecognized mechanism that spatiotemporally coordinates the formation of both lamellipodium/invadopodia and nascent cell-matrix adhesions for directional migration and tumor invasion/metastasis. The unique traits of upregulation and membrane targeting of CLIC1 in cancer cells make it an excellent therapeutic target for tumor metastasis.
Indexed as
Identifiers
What OpenQuestion holds
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.