Norepinephrine transporter promotes the invasion of human colon cancer cells

Epidemiological studies suggested the use of antidepressants to be associated with decreased risk of colorectal cancer (CRC). However, the underlying mechanism through which this decreased risk occurs remains elusive. The norepinephrine transporter (NET) is a target of antidepressants that maintains noradrenergic transmission homeostasis; however, little is known about its function in human CRC cells. The present study, using public datasets and immunohistochemistry approaches, revealed that NET was highly expressed in human CRC tissues with metastasis and in human colon cancer cells. Furthermore, knockdown of NET inhibited the invasive capability of human colon cancer cells. Additionally, epithelial (E)-cadherin expression was increased and Notch1 signaling was inhibited in NET-depleted colon cancer cells. These findings suggest that NET is highly expressed in human colon cancer, which is associated with the invasion of human colon cancer cells by influencing cell-cell adhesion through the Notch1-E-cadherin pathway. Thus, the present study revealed a novel function for NET and its downstream effectors in colon cancer cells, which will be valuable for future studies in a clinical setting.