Homeobox C8 is a transcriptional repressor of E-cadherin gene expression in non-small cell lung cancer.

Loss of E-cadherin expression is a hallmark of epithelial-mesenchymal transition (EMT) in tumor progression. Because previous findings suggested that homeobox C8 (HOXC8) promotes EMT in non-small-cell lung cancer (NSCLC), we investigated whether E-cadherin is a target of HOXC8 protein. In this study, we report that HOXC8 binds to the E-cadherin promoter and acts as a transcriptional repressor to regulate E-cadherin transcription in NSCLC. We further show that loss of E-cadherin leads to an increase in anchorage-independent growth and migration of NSCLC cells, and the inhibitory effects mediated by HOXC8 knockdown can be largely rescued by reduction of E-cadherin expression, suggesting that the HOXC8-E-cadherin pathway is involved in lung cancer progression. Moreover, analysis of E-cadherin and HOXC8 expression indicates that expression of HOXC8 is strongly correlated with loss of E-cadherin expression, and high HOXC8 / low E-cadherin expression is significantly correlated with poor survival for lung cancer patients. Taken together, these data indicate that E-cadherin is a target gene of HOXC8 and that the loss of E-cadherin promotes the growth and migration of NSCLC.

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