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05 June 2019 : Laboratory Research  

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 Chen1A, Yang Liu1A, Cai-Jian Jiang1B, Yan-Min Chen1C, Hong Li1D, Qin-An Liu1EF*

DOI: 10.12659/MSM.914195

Med Sci Monit 2019; 25:4176-4185

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.

Keywords: Cell Migration Inhibition, Colorectal Neoplasms, Epithelial-mesenchymal transition, Neoplasm Invasiveness, Calcium, Cell Movement, Cell Proliferation, Chloride Channels, Databases, Genetic, Disease Progression, Kaplan-Meier Estimate, Middle Aged, Phosphatidylinositol 3-Kinases, Prognosis, Proto-Oncogene Proteins c-akt, Signal Transduction, transcriptome

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Medical Science Monitor Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416