Unraveling the Mysteries of PAX8 in Reproductive Tract Cancers

Abstract

Paired Box 8 (PAX8) is a lineage-specific transcription factor that has essential roles during embryogenesis and tumorigenesis. The importance of PAX8 in the development of the reproductive system is highlighted by abnormalities observed upon the loss or mutation of this PAX family member. In cancer, PAX8 expression is deregulated in a key set of neoplasms, including those arising from the Müllerian ducts. The roles of PAX8 in oncogenesis are diverse and include epigenetic remodeling, stimulation of proliferation, inhibition of apoptosis, and regulation of angiogenesis. PAX8 can interact with different protein partners during cancer progression and may exhibit significant function-altering alternative splicing. Moreover, expression of PAX8 in cancer can also serve as a biomarker for diagnostic and prognostic purposes. In this review, we focus on the roles of PAX8 in cancers of the reproductive system. Understanding the diverse mechanisms of action of PAX8 in development and oncogenesis may identify new vulnerabilities in malignancies that currently lack effective therapies.

Figure 1:

Unraveling the mysteries of PAX8. Top, representative images of PAX8 immunostaining of normal fallopian tube epithelium (FTSEC = fallopian tube secretory epithelial cells and CIL = ciliated cells) normal ovary (OSE = ovarian surface epithelial cells), and invasive high-grade serous carcinoma (HGSC). Bottom, PAX8 transcript expression levels across different reproductive tract cancers (TCGA dataset). Insertion, graphic representation of PAX8-transcriptional complex highlighting the PAX8 structural domains.