NANOG Promotes Cell Proliferation, Invasion, and Stemness via IL-6/STAT3 Signaling in Esophageal Squamous Carcinoma

• Published in: Technology in cancer research & treatment 2021-01, Vol.20, p.15330338211038492-15330338211038492
• Main Authors: Deng, Li, Zhang, Xinping, Xiang, Xiaocong, Xiong, Rong, Xiao, Dongqin, Chen, Zhu, Liu, Kang, Feng, Gang
• Format: Article
• Language: English
• Subjects: Bcl-x protein; Cell growth; Cell Line, Tumor; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cell Self Renewal - genetics; Cell self-renewal; Disease Susceptibility; Drug resistance; Embryo cells; Enzyme-linked immunosorbent assay; Esophageal cancer; Esophageal Squamous Cell Carcinoma - genetics; Esophageal Squamous Cell Carcinoma - metabolism; Esophageal Squamous Cell Carcinoma - pathology; Esophagus; Gene expression; Humans; Interleukin 6; Interleukin-6 - metabolism; Nanog Homeobox Protein - genetics; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Original; Pluripotency; Polymerase chain reaction; Signal Transduction; Squamous cell carcinoma; Stat3 protein; STAT3 Transcription Factor - metabolism; Stem cell factor; Stem cells; Transcription; Transfection; Tumors; Western blotting
• ISSN: 1533-0346; 1533-0338
• DOI: 10.1177/15330338211038492

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. 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. Conclusion: These results revealed that the expression of NANOG promotes cell proliferation, invasion, and stemness via IL-6/STAT3 signaling in ESCC.