ArticlePloS one2013
The transition from proliferation to differentiation in colorectal cancer is regulated by the calcium activated chloride channel A1.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 104 citations in OpenAlex.
- The impact of disease and species differences on the intestinal CLCA4 gene expression.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Comprehensive bioinformatics analysis was used to identify and verify differentially expressed genes in targeted therapy of colon cancer.Scientific reports · 2025Article
- Disulfidptosis-based molecular clustering and prognostic signatures predict patient survival and the immune landscape in patients with colon cancer.Discover oncology · 2025Article
- The CLCA1/TMEM16A/Cl- current axis associates with H2S deficiency in diabetic kidney injury.JCI insight · 2025Article
- Multiomic analysis of familial adenomatous polyposis reveals molecular pathways associated with early tumorigenesis.Nature cancer · 2024Article
- Efficacy of Butyrate to Inhibit Colonic Cancer Cell Growth Is Cell Type-Specific and Apoptosis-Dependent.Nutrients · 2024Article
- Weighted gene co-expression network analysis for hub genes in colorectal cancer.Pharmacological reports : PR · 2024Article
- Regulation of myogenesis and adipogenesis by the electromagnetic perceptive gene.Scientific reports · 2023Article
- Identification of GUCA2A and COL3A1 as prognostic biomarkers in colorectal cancer by integrating analysis of RNA-Seq data and qRT-PCR validation.Scientific reports · 2023Article
- O-Glycomic and Proteomic Signatures of Spontaneous and Butyrate-Stimulated Colorectal Cancer Cell Line Differentiation.Molecular & cellular proteomics : MCP · 2023Article
- Panomics reveals patient individuality as the major driver of colorectal cancer progression.Journal of translational medicine · 2023Article
- Science CommuniCaCells · 2022Review
- Mathematical modelling identifies conditions for maintaining and escaping feedback control in the intestinal epithelium.Scientific reports · 2022Article
- <em>miR-19a</em> targeting <em>CLCA4</em> to regulate the proliferation, migration, and invasion of colorectal cancer cells.European journal of histochemistry : EJH · 2022Article
- Chloride Channels and Transporters: Roles beyond Classical Cellular Homeostatic pH or Ion Balance in Cancers.Cancers · 2022Review
- Identification of Hub Genes in Colorectal Adenocarcinoma by Integrated Bioinformatics.Frontiers in cell and developmental biology · 2022Article
- Association of four genetic variants with colorectal cancer in Kazakhstan population.Oncotarget · 2021Article
- Prognostic value of tumor immune cell infiltration patterns in colon adenocarcinoma based on systematic bioinformatics analysis.Cancer cell international · 2021Article
- Chloride channel accessory 1 integrates chloride channel activity and mTORC1 in aging-related kidney injury.Aging cell · 2021Article
- ETV4 plays a role on the primary events during the adenoma-adenocarcinoma progression in colorectal cancer.BMC cancer · 2021Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breaking the balance between proliferation and differentiation in animal cells can lead to cancer, but the mechanisms maintaining this balance remain largely undefined. The calcium activated chloride channel A1 (CLCA1) is a member of the calcium sensitive chloride conductance family of proteins and is expressed mainly in the colon, small intestine and appendix. We show that CLCA1 plays a functional role in differentiation and proliferation of Caco-2 cells and of intestinal tissue. Caco-2 cells spontaneously differentiate either in confluent culture or when treated with butyrate, a molecule present naturally in the diet. Here, we compared CLCA1 expressional levels between patients with and without colorectal cancer (CRC) and determined the functional role of CLCA1 in differentiation and proliferation of Caco-2 cells. We showed that: 1) CLCA1 and CLCA4 expression were down-regulated significantly in CRC patients; 2) CLCA1 expression was up-regulated in Caco-2 cells induced to differentiate by confluent culture or by treatment with sodium butyrate (NaBT); 3) Knockdown of CLCA1 with siRNA significantly inhibited cell differentiation and promoted cell proliferation in Caco-2 confluent cultures, and 4) In Caco-2 3D culture, suppression of CLCA1 significantly increased cell proliferation and compromised NaBT-induced inhibition of proliferation. In conclusion, CLCA1 may contribute to promoting spontaneous differentiation and reducing proliferation of Caco-2 cells and may be a target of NaBT-induced inhibition of proliferation and therefore a potential diagnostic marker for CRC prognosis.
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