Abstract
High-grade serous ovarian cancer is a deadly disease that can originate from the fallopian tube or the ovarian surface epithelium. The PAX (paired box) genes PAX2 and PAX8 are lineage-specific transcription factors required during development of the fallopian tube but not in the development of the ovary. PAX2 expression is lost early in serous cancer progression, while PAX8 is expressed ubiquitously. These proteins are implicated in migration, invasion, proliferation, cell survival, stem cell maintenance, and tumor growth. Hence, targeting PAX2 and PAX8 represents a promising drug strategy that could inhibit these pro-tumorigenic effects. In this review, we examine the implications of PAX2 and PAX8 expression in the cell of origin of serous cancer and their potential efficacy as drug targets by summarizing their role in the molecular pathogenesis of ovarian cancer.
Highlights
In 2017, there were 22,440 new cases of ovarian cancer and 14,080 deaths [1]
While most cell lines and tumors in this study clustered in the epithelial group, suggesting a fallopian tube cell of origin, the authors identified a subset of cell lines and one High-grade serous carcinoma (HGSC) tumor that grouped in the mesenchymal category, suggesting an ovarian cell of origin [38]
PAX2 and PAX8 are co-expressed during mesenchymal-to-epithelial transition of the Müllerian duct and they continue to be expressed in adult structures, such as the fallopian tube
Summary
In 2017, there were 22,440 new cases of ovarian cancer and 14,080 deaths [1]. Ovarian cancer is the fifth leading cause of cancer related death in women and the most lethal gynecological malignancy. High-grade serous carcinoma (HGSC) accounts for 80% of ovarian cancer cases and it is the deadliest histological subtype of epithelial ovarian cancer (EOC). This high mortality rate is due in part to the insidious nature of the disease, as the majority of cases are detected at an advanced stage with distant metastases. While it was originally believed that the ovary was the primary site of HGSC development, accumulating histologic, molecular, and animal model evidence suggests that the majority of cases originate from the fallopian tube epithelium [4,5,6,7]. Studying PAX2 and PAX8 in this context provides valuable insight into the site of origin of ovarian cancer and the tumorigenic properties that make the PAX proteins promising drug targets for treatment of HGSC
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