FOXD3 regulates anaplastic thyroid cancer progression

Anaplastic thyroid cancer (ATC) is an aggressive malignancy with poor prognosis. It was reported that Forkhead box D3 (FOXD3) transcription factor is associated with several cancers. We investigated its antitumorigenic role of ATC in this study. The ATC cell lines SW1736 and K18 exhibited lower FOXD3 expression than the Nthy-ori-3-1 normal thyroid cell line. FOXD3 downregulation in ATC cell lines promoted invasiveness and epithelial-to-mesenchymal transition (EMT) and decreased cellular apoptosis. FOXD3 silencing also enhanced p-ERK levels in the ATC cell lines, suggesting it negatively regulated MAPK/ERK signaling. Silencing FOXD3 in SW1736 cells also led to generation of larger xenograft tumors with high p-ERK and low E-cadherin levels. Moreover, human ATC samples showed lower FOXD3 and higher p-ERK levels than samples of normal thyroid tissue. These findings demonstrate that FOXD3 acts as a tumor suppressor during anaplastic thyroid carcinogenesis and highlight its potential for clinical application.