Bulk RNAseq of FNE1 cells with ectopic expression of YAP1 and HPV E6/E7 oncogenes

High grade serous ovarian carcinoma (HGSOC) is the most common and aggressive ovarian malignancy. Accumulating evidence indicates that HGSOC may originate from human fallopian tube epithelial cells (FTECs), although the exact pathogen(s) and/or molecular mechanism underlying the malignant transformation of FTECs is unclear. Here we show that human papillomavirus (HPV), which could reach FTECs via retrograde menstruation or sperm-carrying, interacts with the yes-associated protein 1 (YAP1) to drive the initiation and progression of high grade serous cancer (HGSC). HPV prevents FTECs from natural replicative and YAP1-induced senescence, thereby promoting YAP1-induced malignant Transformation of FTECs. HPV also stimulates proliferation and drives metastasis of YAP1-transformed FTECs. YAP1, in turn, stimulates the expression of the putative HPV receptors and suppresses the innate immune system to facilitate HPV acquisition. These findings provide critical clues for developing new strategies to prevent and treat HGSOC. FNE1 cells were cultured to 40% confluent and then transfected with retrovirus-based empty control vector (MXIV), or vectors expressing wild type of YAP1 (YAP), or constitutively active YAP1 (YAPS127A, a replacement of Serine at residue 127 with Alanine resulting in the constitutive activation of YAP1 protein [66]). All transfected cells were selected with G418 (200-400μg/ml). YAP1 expression in these cells was confirmed by RT-PCR and Western blot.