TWIST1 plays a pleiotropic role in determining the anaplastic thyroid cancer phenotype.

CONTEXT Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human tumors; it is characterized by chemoresistance, local invasion, and distant metastases. ATC is invariably fatal. OBJECTIVE The aim was to study the role of TWIST1, a basic helix-loop-helix transcription factor, in ATC. DESIGN Expression of TWIST1 was studied by immunohistochemistry and real-time PCR in normal thyroids and well-differentiated, poorly differentiated, and ATC. The function of TWIST1 was studied by RNA interference in ATC cells and by ectopic expression in well-differentiated thyroid carcinoma cells. RESULTS ATCs up-regulate TWIST1 with respect to normal thyroids as well as to poorly and well-differentiated thyroid carcinomas. Knockdown of TWIST1 by RNA interference in ATC cells reduced cell migration and invasion and increased sensitivity to apoptosis. The ectopic expression of TWIST1 in thyroid cells induced resistance to apoptosis and increased cell migration and invasion. CONCLUSIONS TWIST1 plays a key role in determining malignant features of the anaplastic phenotype in vitro.