Mechanisms of induction of HIF-1α and downstream effects of HIF-1 signalling in thyroid carcinomas. HIF-1 activity is induced not only by hypoxia but by the oncogenic MAPK and PI3K signalling pathways. Clinically, expression of HIF-1α and the downstream target CA-9 have been linked with thyroid carcinoma aggressiveness. It is well known that HIF-1 plays an important role in tumour development, metastasis, and aggressiveness and is ultimately correlated with poor prognosis. Enhanced HIF-1 signalling by hypoxia and the PI3K/MAPK pathways may play an important role in the metastatic characteristics of thyroid carcinoma. HIF-1-induced MET upregulation has been implicated in promoting invasiveness of PTC. HIF-1 signalling may also play a prominent role in the therapeutic response to radiotherapy in thyroid carcinoma.
