Paired box protein Pax-8 (PAX8)

Paired box protein Pax-8 (PAX8) is a transcription factor belonging to the paired box (PAX) family, which plays a key role in organogenesis and cell differentiation, particularly in the thyroid gland, kidney, and reproductive tract[1][3][4][6]. PAX8 regulates thyroid-specific gene expression, is required for thyroid hormone synthesis, and is essential for the development and maintenance of thyroid follicular cells, as well as the formation of the kidney and Müllerian system during embryogenesis[1][2][3]. In cancer, overexpression, mutation, or chromosomal rearrangements (e.g., PAX8-PPARγ fusion) are implicated in thyroid, renal, and Müllerian tumors[1][2][4][6]. PAX8 is widely used as an immunohistochemical biomarker in the diagnosis of several carcinomas[6]. There are currently no approved direct drugs targeting wild-type PAX8, but the fusion PAX8-PPARγ protein in thyroid cancer can be affected by PPARγ ligands (under study)[2]. Targeting PAX8 function presents significant therapeutic and safety challenges due to its broad role in developmental and homeostatic processes.

Other names

Paired box gene 8PAX-8paired domain gene 8paired box protein Pax-8

Inhibition of transcriptional activity (by RNA interference) Disruption of fusion protein (PAX8-PPARγ) function with PPARγ modulators