Background
Cancer cells have properties similar to those of stem cells, including high proliferation and self-renewal ability. NANOG is the key regulatory gene that maintains the self-renewal and pluripotency characteristics of embryonic stem cells. We previously reported that knockdown of the pluripotent stem cell factor NANOG obviously reduced the proliferation and drug-resistance capabilities of esophageal squamous cell carcinoma (ESCC). In this study, we gained insights into the potential regulatory mechanism of NANOG, particularly in ESCC.
Conclusion
These results revealed that the expression of NANOG promotes cell proliferation, invasion, and stemness via IL-6/STAT3 signaling in ESCC.
Methods
NANOG was ectopically expressed in the Eca-109 cell line via pcDNA3.1 vector transfection. The mRNA expression of different genes was detected using quantitative real-time polymerase chain reaction, and protein quantification was performed by western blotting. The enzyme-linked immunosorbent assay was used to detect the expression of interleukin 6 (IL-6). The capabilities of proliferation, migration, and invasion were investigated using cell count and Transwell assays. The tumor sphere-forming assay was used to investigate the sphere formation capacity of cancer stem cells.
Results
The expression of NANOG promoted the cell proliferation and sphere formation capacity of cancer stem cells in a dose-dependent manner. IL-6-mediated activation of signal transducer and activator of transcription 3 (STAT3) was closely related to the expression of NANOG in ESCC. Consistently, the target genes of STAT3, including CCL5, VEGFA, CCND1, and Bcl-xL, were upregulated upon the overexpression of NANOG.