Role of Sonic Hedgehog signaling in thyroid tumorigenesis and tumor-stroma interaction

Thyroid carcinomas represent the most common endocrine cancers with their incidence increasing worldwide. Up to date there are no efficient treatments for patients affected by metastatic thyroid disease that is not responsive to radioiodine treatment. Sonic Hedgehog (Shh) pathway is active in regulating embryonic development of different organs as well as of the thyroid gland. The aberrant activation of Shh signaling has been found in several types of cancer and, according to recent evidences, it represents an important regulator of tumor- stroma interaction. In this dissertation, we have studied expression, activation and molecular mechanisms regulating the Shh pathway in thyroid cancer and its involvement in the modulation of tumor stroma interaction in anaplastic thyroid cancer cells (ATC). Our results suggest that Shh signaling is activated through different mechanisms in thyroid cancer cells: in a non-canonical way in cooperation with other oncogenic pathways to promote and support thyroid neoplastic transformation as well as in a paracrine way in tumor-stroma interaction, supporting thyroid cancer cells invasion and migration. Our data therefore suggest that Shh signaling could be a novel therapeutic target in aggressive thyroid cancers.