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pmid:31164625

Calcium-Activated Chloride Channel A4 (CLCA4) Plays Inhibitory Roles in Invasion and Migration Through Suppressing Epithelial-Mesenchymal Transition via PI3K/AKT Signaling in Colorectal Cancer.

Hua Chen · Yang Liu · Cai-Jian Jiang · Yan-Min Chen · Hong Li · Qin-An Liu

Medical science monitor : international medical journal of experimental and clinical research · 2019 doi:10.12659/MSM.914195

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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title
Calcium-Activated Chloride Channel A4 (CLCA4) Plays Inhibitory Roles in Invasion and Migration Through Suppressing Epithelial-Mesenchymal Transition via PI3K/AKT Signaling in Colorectal Cancer.
doi
10.12659/MSM.914195
pmid
31164625
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[0]
Hua Chen
[1]
Yang Liu
[2]
Cai-Jian Jiang
[3]
Yan-Min Chen
[4]
Hong Li
[5]
Qin-An Liu
journal
Medical science monitor : international medical journal of experimental and clinical research
year
2019
abstract
BACKGROUND Calcium-activated chloride channel A4 (CLCA4) is known as a tumor suppressor which contributes to the progression of a number of types of malignant tumors. However, little is known about the functional roles of CLCA4 in colorectal cancer (CRC). MATERIAL AND METHODS In this study, the expression patterns and dysregulation of mRNAs in CRC tissues were profiled by analyzing GSE21510 datasets from Gene Expression Omnibus database which contains 104 primary hepatocellular carcinoma tissues and 24 normal liver tissues, and by performing Kaplan-Meier analysis of TCGA data. Additionally, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) were performed using clinical tissues collected at our institute. In order to explore the functional role of CLCA4, gain-of-function cell models were constructed in SW620 and LoVo cells. Wound healing assay and Transwell assay were carried out to access the cell migration and invasion ability. RESULTS It was found that CLCA4 was an independent predictor for overall survival and lymph node metastasis. Additionally, immunohistochemistry and qRT-PCR results of the clinical tissues collected as part of our study further confirmed this correlation. In vitro experiments demonstrated that over-expression of CLCA4 could inhibit cell migration and invasion by suppressing epithelial-mesenchymal transition (EMT) via PI3K/ATK signaling and change the expression patterns of EMT markers in CLCA4-gain-of-function cell models. CONCLUSIONS CLCA4 inhibits migration and invasion by suppressing EMT via PI3K/ATK signaling and predicts favorable prognosis of CRC which may help to distinguish potential risk of lymph node metastasis in CRC.
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Clinical Significance of Osteoprotegerin Expression in Human Colorectal Cancer
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31164625", "kind": "science-record", "revision": 8, "content_hash": "sha256:8096cd9437e2527434db2c830b4a2500e616c10a102f266fb50bd01ac27ff745", "created_at": "2026-11-01T15:40:45Z", "updated_at": "2026-11-01T22:00:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Calcium-Activated Chloride Channel A4 (CLCA4) Plays Inhibitory Roles in Invasion and Migration Through Suppressing Epithelial-Mesenchymal Transition via PI3K/AKT Signaling in Colorectal Cancer.", "doi": "10.12659/MSM.914195", "pmid": "31164625", "authors": ["Hua Chen", "Yang Liu", "Cai-Jian Jiang", "Yan-Min Chen", "Hong Li", "Qin-An Liu"], "journal": "Medical science monitor : international medical journal of experimental and clinical research", "year": 2019, "abstract": "BACKGROUND Calcium-activated chloride channel A4 (CLCA4) is known as a tumor suppressor which contributes to the progression of a number of types of malignant tumors. However, little is known about the functional roles of CLCA4 in colorectal cancer (CRC). MATERIAL AND METHODS In this study, the expression patterns and dysregulation of mRNAs in CRC tissues were profiled by analyzing GSE21510 datasets from Gene Expression Omnibus database which contains 104 primary hepatocellular carcinoma tissues and 24 normal liver tissues, and by performing Kaplan-Meier analysis of TCGA data. Additionally, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) were performed using clinical tissues collected at our institute. In order to explore the functional role of CLCA4, gain-of-function cell models were constructed in SW620 and LoVo cells. Wound healing assay and Transwell assay were carried out to access the cell migration and invasion ability. RESULTS It was found that CLCA4 was an independent predictor for overall survival and lymph node metastasis. Additionally, immunohistochemistry and qRT-PCR results of the clinical tissues collected as part of our study further confirmed this correlation. In vitro experiments demonstrated that over-expression of CLCA4 could inhibit cell migration and invasion by suppressing epithelial-mesenchymal transition (EMT) via PI3K/ATK signaling and change the expression patterns of EMT markers in CLCA4-gain-of-function cell models. CONCLUSIONS CLCA4 inhibits migration and invasion by suppressing EMT via PI3K/ATK signaling and predicts favorable prognosis of CRC which may help to distinguish potential risk of lymph node metastasis in CRC.", "claims": [{"id": "claim-method", "statement": "Overall survival (OS) was calculated using the Kaplan-Meier method; P<0.05 was considered significant differences.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31164625", "locator": "sections[8] \"Statistical analysis\" paragraph 2", "quote": "Overall survival (OS) was calculated using the Kaplan-Meier method; P<0.05 was considered significant differences."}], "state": "complete"}, {"id": "claim-data-access", "statement": "we explored GSE21510 dataset containing mRNA expression profiles of 104 CRC tissues and 24 noncancerous tissues", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31164625", "locator": "sections[10] \"CLCA4 was decreased in CRC tissues compared with normal tissues in TCGA\" paragraph 2", "quote": "we explored GSE21510 dataset containing mRNA expression profiles of 104 CRC tissues and 24 noncancerous tissues"}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:31164625"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE21510"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE21510"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31164625", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.12659/MSM.914195", "sha256": 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