Dickkopf-1 (DKK1) controls papillary and follicular thyroid cancer growth.

Abstract

Thyroid cancer, the most frequent endocrine tumor, has a good prognosis. However, the survival rate of patients with recurrent or metastatic forms that become resistant to conventional treatments drops to <20% at 10 years, with a mean life expectancy of 3-5 years. The molecular mechanisms that drive the advancement of these forms are still largely unknown, and therefore, the identification of disease progression biomarkers is of great clinical relevance. Dickkopf-1 (DKK1) is a regulator of the Wnt signaling cascade that controls several biological processes, including cell proliferation, differentiation, and migration. DKK1 has been associated with progression and poor prognosis in different types of tumors; however, its role in thyroid cancer is still not well defined, and a better characterization is needed. The present study investigated the role of DKK1 in the growth of papillary and follicular thyroid cancers in in vitro and in vivo models. In vitro, DKK1 silencing through siRNA and deletion via CRISPR/Cas9 editing were performed in different papillary and follicular thyroid cancer cell lines. Both silencing and deletion reduced cell growth and migration, with the involvement of β-catenin-dependent Wnt and PI3K/mTOR pathways. In vivo xenograft tumor models showed that DKK1 deletion reduced tumor growth. In conclusion, our findings support the key role of DKK1 in the growth of differentiated thyroid cancers both in vitro and in vivo.