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Pax8: A Unifying Target for Serous Tumors

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Technical Report,15 Apr 2017,14 Apr 2019

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University of Illinois at Chicago Chicago United States

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High-grade serous cancer HGSC may arise from the ovarian surface epithelium OSE or the fallopian tube epithelium FTE. The paired-box transcription factor 8 PAX8 is a transcription factor involved in the differentiation of Mllerian derived cells. The OSE does not express PAX8, but PAX8 is expressed in approximately 80-96 percent of HGSC. Intriguingly, murine models of HGSC derived from the OSE acquire PAX8, suggesting that it is not only a marker of Mllerian origin, but also an essential part of cancer progression, potentially from both the OSE and FTE. Importantly, previous studies suggest that PAX8 expression is essential for the survival of HGSC regardless of source. Our preliminary data suggests that PAX8 loss in HGSC induces apoptosis, regulates migration, FOXM1, and angiogenesis. Targeting PAX8 may impact multiple aspects of ovarian cancer physiology and tumors derived from both OSE and FTE. Our preliminary data also indicates that reduction of PAX8 in normal oviductal cells does not significantly impact their survival, thus making it an interesting drug target. Our hypothesis is that PAX8 is an essential transcription factor for survival of HGSC regardless of cell of origin and blocking its expression may provide a new strategy for impacting both tumor cells and the microenvironment.

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  • Medicine and Medical Research

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