EMBO reports · 2024
HPV-YAP1 oncogenic alliance drives malignant transformation of fallopian tube epithelial cells.
СтатьяНазвание и аннотация: Перевод в очереди
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He Chunbo, Lv Xiangmin, Liu Jiyuan, Ruan Jinpeng, Chen Peichao, Huang Cong, Angeletti Peter C, Hua Guohua, Moness Madelyn Leigh, Shi Davie, Dhar Anjali, Yang Siyi, Murphy Savannah, Montoute Isabelle, Chen Xingcheng, Islam Kazi Nazrul, George Sophia, Ince Tan A, Drapkin Ronny, Guda Chittibabu, Davis John S, Wang Cheng
Аннотация
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 malignant transformation of FTECs. 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.