HPV-YAP1 oncogenic alliance drives malignant transformation of fallopian tube epithelial cells
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.
Authors
- Sophia H.L. George (ORCID: https://orcid.org/0000-0003-1013-1883)
- Guohua Hua (ORCID: https://orcid.org/0000-0002-6900-1023)
- Cong Huang (ORCID: https://orcid.org/0000-0002-2307-864X)
- Tan A. Ince (ORCID: https://orcid.org/0000-0003-0315-6425)
- Kazi Nazrul Islam (ORCID: https://orcid.org/0000-0002-7706-7225)
- Xingcheng Chen
- Peichao Chen (ORCID: https://orcid.org/0000-0001-9587-7080)
- Davie Shi (ORCID: https://orcid.org/0009-0003-0498-6321)
- Chittibabu Guda (ORCID: https://orcid.org/0000-0002-5393-9316)
- John S. Davis (ORCID: https://orcid.org/0000-0003-3468-4079)
- Ronny Drapkin (ORCID: https://orcid.org/0000-0002-6912-6977)
- Peter C. Angeletti
- Madelyn L. Moness
- Chunbo He (ORCID: https://orcid.org/0000-0001-8250-1092)
- Jinpeng Ruan
- Cheng Wang (ORCID: https://orcid.org/0000-0002-0911-8254)
- Jiyuan Liu (ORCID: https://orcid.org/0000-0002-0372-4106)
- Siyi Yang
- Isabelle Montoute
- Anjali Dhar
- Xiangmin Lv
- Savannah Murphy
Institutions
- University of Nebraska–Lincoln (US)
- Nebraska Medical Center (US)
- NewYork–Presbyterian Brooklyn Methodist Hospital (US)
- Harvard University (US)
- Xiamen University (CN)
- Huazhong Agricultural University (CN)
- Cornell University (US)
- St Vincent Hospital (US)
- Massachusetts General Hospital (US)
- Omaha VA Medical Center (US)
- VA Nebraska Western Iowa Health Care System (US)
- Sylvester Comprehensive Cancer Center (US)
- University of Nebraska Medical Center (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- EMBO Reports
- Published
- 2024-09-13
- DOI
- https://doi.org/10.1038/s44319-024-00233-3
- Citations
- 5
- Primary Topic
- Hippo pathway signaling and YAP/TAZ
- Type
- article
- Field-Weighted Citation Impact
- 1.63
Funders
- University of Nebraska Medical Center
- Fred and Pamela Buffett Cancer Center
- National Cancer Institute