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
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Mentions: A mouse xenograft tumor model was used to determine the effects of YAP on the progression of cervical cancer in vivo. The results showed that in comparison with ME180-MXIV cells, tumors derived from ME180-YAP and ME180-YAPS127A cells were larger and detected earlier. On day 23 of tumor growth, the tumor volumes (mm3, mean ± SEM, n = 6) of the ME180-YAP group (952.5 ± 124.3) and the ME180-YAPS127A group (963.1 ± 232.6) were significantly larger than that of the ME180-MXIV group (236.8 ± 23.4) (P < 0.01) (Fig4A–D). The weights of the tumors in the YAP and YAPS127A groups were also significantly higher than those of the control group (n = 6, P < 0.001, Fig4E). Western blot analysis confirmed the overexpression of YAP protein in both ME180-YAP and ME180-YAPS127A tumor xenografts (Fig4F). Fluorescent immunohistochemistry clearly indicated that tumor tissues derived from ME180-YAP and ME180-YAPS127A tumor xenografts had higher expression of Ki67, a known cell proliferation marker, confirming our in vitro observations that YAP regulates the proliferation of cervical cancer cells in vivo (Fig4G, Appendix Fig S8).
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.