AREG Upregulation in Cancer Cells via Direct Interaction with Cancer-Associated Fibroblasts Promotes Esophageal Squamous Cell Carcinoma Progression Through EGFR-Erk/p38 MAPK Signaling.
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引用次数: 0
Abstract
Cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment and significantly contribute to the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). Our previous study established a direct co-culture system of human bone marrow-derived mesenchymal stem cells (progenitors of CAFs) and ESCC cell lines, which facilitates the generation of CAF-like cells and enhances malignancy in ESCC cells. In this study, we further elucidated the mechanism by which CAFs promote ESCC progression using cDNA microarray analysis of monocultured ESCC cells and those co-cultured with CAFs. We observed an increase in the expression and secretion of amphiregulin (AREG) and the expression and phosphorylation of its receptor EGFR in co-cultured ESCC cells. Moreover, AREG treatment of ESCC cells enhanced their survival and migration via the EGFR-Erk/p38 MAPK signaling pathway. Immunohistochemical analysis of human ESCC tissues showed a positive correlation between the intensity of AREG expression at the tumor-invasive front and the expression level of the CAF marker FAP. Bioinformatics analysis confirmed significant upregulation of AREG in ESCC compared with normal tissues. These findings suggest that AREG plays a crucial role in CAF-mediated ESCC progression and could be a novel therapeutic target for ESCC.
CellsBiochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
9.90
自引率
5.00%
发文量
3472
审稿时长
16 days
期刊介绍:
Cells (ISSN 2073-4409) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to cell biology, molecular biology and biophysics. It publishes reviews, research articles, communications and technical notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided.