LAUSR

PAX8 is a master transcription factor that is essential during embryogenesis and promotes neoplastic growth. It is expressed by the secretory cells lining the female reproductive tract, and its deletion during development results in atresia of reproductive tract organs. Nearly all ovarian carcinomas express PAX8, and its knockdown results in apoptosis of ovarian cancer cells. To explore the role of PAX8 in these tissues, we purified the PAX8 protein complex from nonmalignant fallopian tube cells and high-grade serous ovarian carcinoma cell lines. We found that PAX8 was a member of a large chromatin remodeling complex and preferentially interacted with SOX17, another developmental transcription factor. Depleting either PAX8 or SOX17 from cancer cells altered the expression of factors involved in angiogenesis and functionally disrupted tubule and capillary formation in cell culture and mouse models. PAX8 and SOX17 in ovarian cancer cells promoted the secretion of angiogenic factors by suppressing the expression of SERPINE1, which encodes a proteinase inhibitor with antiangiogenic effects. The findings reveal a non–cell-autonomous function of these transcription factors in regulating angiogenesis in ovarian cancer. Description A complex of the transcription factors PAX8 and SOX17 in ovarian tumors mediates proangiogenic effects. A PAX8-SOX17 duo in tumor angiogenesis The transcription factor PAX8 is essential for the development of the female reproductive tract but is frequently amplified in and supports the growth of ovarian cancers. By comparing ovarian cancer and nonmalignant fallopian tube cells and tissues, Chaves-Moreira et al. found that PAX8 interacted with another transcription factor, SOX17, and that this complex in cancer cells transcriptionally promoted a proangiogenic secretome, which involved a decrease in plasminogen activator inhibitor 1 and an increase in factors like VEGF. Repressing the complex inhibited tumor cell–induced angiogenesis in both cell culture and in vivo models. The findings may facilitate antiangiogenic strategies for treating ovarian cancer.