NKX6.3 Is a Transcription Factor for Wnt/β-catenin and Rho-GTPase Signaling-Related Genes to Suppress Gastric Cancer Progression

• NKX6.3 loss is associated with metastasis and poor survival in gastric cancer.
• NKX6.3 transcriptionally inhibits Wnt/β-catenin and Rho-GTPase family induced migration and invasion.
• NKX6.3 inactivation is critical for gastric cancer cell invasion and metastasis.Yoon et al. reveal that NKX6.3 prevents EMT and cell migration through transcriptionally modulates the expression of Wnt/β-catenin and Rho-GTPase pathway-related genes, implying that NKX6.3 inactivation might be one of the key mechanisms of gastric cancer cell invasion and metastasis.

Despite ongoing research and recent progress, the prognosis for patients with advanced gastric cancer remains poor. Wnt/β-catenin and Rho-GTPase signaling pathways are known to play essential roles in malignant transformation and progression of various tumors, including gastric cancer. Here, we identify that NKX6 transcription factor, locus 3 (NKX6.3) binds directly to specific promoter regions of Wnt/β-catenin and Rho-GTPase pathway-related genes, resulting in inhibition of cancer cell migration and invasion. Additionally, we find that the expression level of NKX6.3 is involved in regulation of gastric cancer progression and expression of Wnt/β-catenin and Rho-GTPase pathway-related genes in clinical samples. These results suggest that NKX6.3 prevents EMT and cell migration, implying that NKX6.3 inactivation might be one of the key mechanisms of gastric cancer cell invasion and metastasis.

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