ArticlePloS one2016
CLCA2 Interactor EVA1 Is Required for Mammary Epithelial Cell Differentiation.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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
28 citing papers in PubMed, 47 citations in OpenAlex.
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- Loss of Predicted Cell Adhesion Molecule MPZL3 Promotes EMT in Ovarian Cancer.Cancer research communications · 2025Article
- Hearing restoration by gene replacement therapy for a multisite-expressed gene in a mouse model of human DFNB111 deafness.American journal of human genetics · 2024Article
- Transport of CLCA2 to the nucleus by extracellular vesicles controls keratinocyte survival and migration.Journal of extracellular vesicles · 2024Article
- TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2.Journal of ovarian research · 2024Article
- Article
- FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer.International journal of molecular sciences · 2023Review
- CLCA2 overexpression suppresses epithelial-to-mesenchymal transition in cervical cancer cells through inactivation of ERK/JNK/p38-MAPK signaling pathways.BMC molecular and cell biology · 2022Article
- The role of human antigen R (HuR) in modulating proliferation, senescence and radiosensitivity of skin cells.Experimental and therapeutic medicine · 2022Article
- WNT5A promotes the metastasis of esophageal squamous cell carcinoma by activating the HDAC7/SNAIL signaling pathway.Cell death & disease · 2022Article
- A basement membrane discovery pipeline uncovers network complexity, regulators, and human disease associations.Science advances · 2022Article
- Article
- Gene network analysis to determine the effect of hypoxia-associated genes on brain damages and tumorigenesis using an avian model.Journal, genetic engineering & biotechnology · 2021Article
- CLCA2 suppresses the proliferation, migration and invasion of cervical cancer.Experimental and therapeutic medicine · 2021Article
- Epigenetic Repression of Chloride Channel Accessory 2 Transcription in Cardiac Fibroblast: Implication in Cardiac Fibrosis.Frontiers in cell and developmental biology · 2021Article
- Microenvironment Stiffness Amplifies Post-ischemia Heart Regeneration in Response to Exogenous Extracellular Matrix Proteins in Neonatal Mice.Frontiers in cardiovascular medicine · 2021Article
- Epithelial V-like antigen 1 promotes hepatocellular carcinoma growth and metastasis via the ERBB-PI3K-AKT pathway.Cancer science · 2020Article
- Prognostic value of chloride channel accessory mRNA expression in colon cancer.Oncology letters · 2019Article
- Emerging roles for multifunctional ion channel auxiliary subunits in cancer.Cell calcium · 2019Review
- Transcriptional Analysis of Immunohistochemically Defined Subgroups of Non-Muscle-Invasive Papillary High-Grade Upper Tract Urothelial Carcinoma.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
CLCA2 is a p53-, p63-inducible transmembrane protein that is frequently downregulated in breast cancer. It is induced during differentiation of human mammary epithelial cells, and its knockdown causes epithelial-to-mesenchymal transition (EMT). To determine how CLCA2 promotes epithelial differentiation, we searched for interactors using membrane dihybrid screening. We discovered a strong interaction with the cell junctional protein EVA1 (Epithelial V-like Antigen 1) and confirmed it by co-immunoprecipitation. Like CLCA2, EVA1 is a type I transmembrane protein that is regulated by p53 and p63. It is thought to mediate homophilic cell-cell adhesion in diverse epithelial tissues. We found that EVA1 is frequently downregulated in breast tumors and breast cancer cell lines, especially those of mesenchymal phenotype. Moreover, knockdown of EVA1 in immortalized human mammary epithelial cells (HMEC) caused EMT, implying that EVA1 is essential for epithelial differentiation. Both EVA1 and CLCA2 co-localized with E-cadherin at cell-cell junctions. The interacting domains were delimited by deletion analysis, revealing the site of interaction to be the transmembrane segment (TMS). The primary sequence of the CLCA2 TMS was found to be conserved in CLCA2 orthologs throughout mammals, suggesting that its interaction with EVA1 co-evolved with the mammary gland. A screen for other junctional interactors revealed that CLCA2 was involved in two different complexes, one with EVA1 and ZO-1, the other with beta catenin. Overexpression of CLCA2 caused downregulation of beta catenin and beta catenin-activated genes. Thus, CLCA2 links a junctional adhesion molecule to cytosolic signaling proteins that modulate proliferation and differentiation. These results may explain how attenuation of CLCA2 causes EMT and why CLCA2 and EVA1 are frequently downregulated in metastatic breast cancer cell lines.
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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.