Translational Highlights from the Endocrine Society Journals

摘要

The following abstracts from the Endocrine Society Journals have been selected by the editors as being particularly relevant to readers interested in translational science. Andrzej A. Dlugosz, Caterina Missero, and Monica Dentice Thyroid hormone (TH) is an important regulator of growth, de- velopment, and metabolism. Most of the active THT; is generated by peripheral TH metabolism mediated by the iodothyronine de- iodinases. Type 3 deiodinase (D3) inactivates T3 via specific deio- dination reactions. It is an oncofetal protein frequently expressed in neoplastic tissues and is a direct target of the sonic hedgehog (Shh) pathway in basal cell carcinomas (BCCs). However, the mo- lecular mechanisms triggered by T; in BCC are still mostly unre- vealed. Here, we demonstrate that D3 action is critical in the proliferation and survival of BCC cells. D3 depletion or T; treat- ment induce apoptosis of BCC cells and attenuate Shh signaling. This is achieved through a direct impairment of Gli2 protein sta- bility by Ts. T, induces PKA, which in turn destabilizes Gli2 protein via its C-terminal degron. Finally, in a mouse model of BCC, T3- topical treatment significantly reduces tumor growth. These re- sults demonstrate the existence of a previously unrecognized cross talk between TH and Gli2 oncogene, providing functional and mechanistic evidence of the involvement of TH metabolism in Shh-induced cancer. TH-mediated Gli2 inactivation would be beneficial for therapeutically purposes, because the inhibition of Shh-Gli2 signaling is an attractive target for several anticancer drugs, currently in clinical trials.