Abstract
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies frequently associated with extrathyroidal extension and metastasis through pathways that remain unclear. Analysis of the cancer genome atlas (TCGA) database and an independent cohort showed that the expression of hematological and neurological expressed 1 (HN1) was higher in thyroid cancers than in normal tissues, and negatively correlated with progression-free survival. RT-PCR and immunohistochemistry revealed higher HN1 expression in ATC compared to healthy tissues and papillary thyroid carcinoma (PTC). HN1 knockdown attenuated migration and invasion of ATC cells, whereas HN1 overexpression increased migration and invasion of PTC cells. HN1 reduced the acetylation of α-tubulin and promoted progression through epithelial-mesenchymal transition of ATC cells and mouse xenografts. HN1 knockdown significantly attenuated TGF-β-induced mesenchymal phenotype, and inhibited tumor formation and growth of ATC xenografts in nude mice. Loss of STMN1 decreased the malignant potential of HN1, whereas HN1 knockdown in combination with STMN1 overexpression restored the aggressive properties of ATC cells. HN1 increased STMN1 mRNA expression, and prevented STMN1 ubiquitination and subsequent degradation. These results demonstrate that HN1 interacts with STMN1 and drives ATC aggressiveness.