The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression.
Bottom Line: The Hippo signaling pathway controls organ size and tumorigenesis through a kinase cascade that inactivates Yes-associated protein (YAP).Our results suggest that YAP expression is associated with a poor prognosis for cervical cancer.Our study indicates that combined targeting of the Hippo and the ERBB signaling pathways represents a novel therapeutic strategy for prevention and treatment of cervical cancer.
Affiliation: Olson Center for Women's Health, Department of Obstetrics & Gynecology, University of Nebraska Medical Center, Omaha, NE, USA College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China.Show MeSH
Related in: MedlinePlus
Mentions: Epidemiological studies have shown that the high-risk HPV E6/E7 protein plays a critical role in the initiation and progression of cervical cancer. However, the exact molecular mechanism underlying the ability of high-risk HPV E6/E7 to regulate cervical cancer is largely unknown. Treatment of HT3 cells (cervical cancer cells without HPV infection) (Fogh et al, 1977; Yee et al, 1985) with HPV16 E6 protein significantly increased cancer cell growth (Fig9A). Surprisingly, treatment of HT3 cells with HPV16 E6 increased protein levels of total YAP and phosphorylated YAP (Ser127), but had no effect on the protein level of β-actin (Fig9B). Real-time PCR results showed that treatment of HT3 cells with HPV16 E6 for 48 h also significantly increased mRNA level of AREG (Fig9C). This finding is consistent with the observed increase in YAP protein levels since AREG is downstream gene of the Hippo/YAP pathway. Knockdown of YAP with YAP siRNA eliminated HPV16 E6-stimulated HT3 cell proliferation (Fig9D and E), further suggesting that YAP is an important mediator of HPV16 E6 action in cervical cancer cells.
Affiliation: Olson Center for Women's Health, Department of Obstetrics & Gynecology, University of Nebraska Medical Center, Omaha, NE, USA College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China.