Since epithelial-mesenchymal transition (EMT)
plays a critical role in cancer progression and in maintaining
cancer stem cell properties, EMT is emerging as a therapeutic
target for inhibiting the metastatic progression of
cancer cells. 20-Hydroxycinnamaldehyde (HCA) and its
derivative, 20-benzoyloxycinnamaldehyde, have recently
been suggested as promising therapeutic candidates for
cancer treatment. The purpose of this study is to investigate
the anti-metastatic effect of HCA on breast cancer and
the molecular mechanisms by which HCA regulates the
transcriptional program during EMT. HCA induces epithelial
reversion at nanomolar concentrations by suppressing
Snail via the nuclear translocalization of GSK-3b, which
results in the transcriptional upregulation of E-cadherin.
HCA also activates the transcription factor KLF17, which
suppresses Id-1, indicating that HCA inhibits EMT by multiple
transcriptional programs. Further, HCA treatment significantly
inhibits lung metastasis in a mouse orthotopic
breast cancer model. This study demonstrates the anti-metastatic
effect of the non-toxic natural compound HCA
through attenuation of EMT in a breast cancer model.