Loss of CDH1 up-regulates epidermal growth factor receptor via phosphorylation of YBX1 in non-small cell lung cancer cells

• We inhibited CDH1 expression in lung cancer cells using siRNA and shRNA.
• CDH1 loss promotes EGFR transcription through YBX1 in lung cancer cells.
• Loss of CDH1 activates downstream effectors of the EGFR signaling pathway.
• YBX1 and EGFR contribute to proliferation and invasiveness promoted by CDH1 loss.

Although loss of CDH1 promotes cancer metastasis by disrupting cell–cell adhesion and inducing transcriptional changes, the functional pathways involved in the loss of CDH1 affecting EGFR expression in lung cancer cells still remain largely unknown. In this study, we report that down-regulation of CDH1 promoted EGFR transcription through activation of YBX1. Furthermore, knockdown of CDH1 activated the AKT signaling pathway, and inhibition of AKT suppressed the phosphorylation of YBX1 and the up-regulation of EGFR induced by CDH1 loss. These data demonstrate that loss of CDH1 induces EGFR expression via phospho-YBX1, which is activated through the AKT signaling pathway.