Figure 5.
Enhancement of epithelial‐to‐mesenchymal transition (EMT) via the loss of N‐myc downstream‐regulated gene 2 (NDRG2) activity. Because loss of NDRG2 expression has been reported to promote cancer development and metastasis, we conducted animal studies in an oral cancer model using NDRG2‐deficient mice. 27 In Ndrg2‐deficient mice, the treatment of carcinogenic compound 4‐nitroquinoline‐1‐oxide (4‐NQO) induces development of oral cancer and cervical lymph node metastasis, which enhances the activation of the PI3K/AKT and nuclear factor kappa B (NF‐κB) signaling pathways via enhanced phosphorylation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) by downregulating NDRG2. Activation of the NF‐κB signaling pathway promotes EMT via the upregulation of twist family bHLH transcription factors (TWIST) and SNAIL family of transcriptional repressors (SNAIL) transcription, which induces metastasis of oral squamous cell carcinoma (OSCC) because intercell adhesion is lost and motility is increased. 27 Therefore, reduced NDRG2 expression contributes to cancer development and metastasis by regulation of EMT. This figure has been adapted from reference27 with permission