Journal
EXPERIMENTAL CELL RESEARCH
Volume 375, Issue 2, Pages 41-50Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2019.01.002
Keywords
Esophageal cancer; Cancer-associated fibroblasts; Twist1; Epithelial-mesenchymal transition
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Funding
- Henan Provincial People's Hospital
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Cancer-associated fibroblasts (CAFs) play critical roles in tumor progression. However, the role and mechanism underlying CAFs in esophageal cancer (EC) remain unclear. In this study, primary CAFs and normal esophageal fibroblasts (NOFs) were isolated and characterized by immunofluorescence, qRT-PCR and western blot. Clinical significance of twist1 in CAFs were evaluated by immunohistochemistry assay. Conditioned medium (CM) was collected from CAFs to evaluate the influence on epitheliaI-mesenchymal transition (EMT) of EC cells. EC cells were mixed with CAFs and subcutaneously injected into nude mice to assess the in vivo tumor growth. As the result, twist was overexpressed in CAFs compared with NOFs and exhibited adverse prognostic significance. In CAFs, twist1 promoted the expression and secretion of CXCL12. In EC cells, activated CXCL12/CXCR4 signaling promoted the EMT process through ERK/AKT - twist1 - MMP1/E-cadherin pathway. In addition, knockdown of twist1 in CAFs also suppressed in vivo tumor growth. In conclusion, our results revealed a dual role of twist1 in CAFs and EC cells to promote the EMT process.
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