Figure 1.

Synergism between YAP1 and HPV oncoproteins plays a central role in cervical carcinogenesis. Research results generated from our in vitro and in vivo experimental models and data derived from multi-dimensional cancer genetic/genomic analyses of TCGA database suggest that the disruption of the Hippo signaling pathway and the subsequent hyperactivation of YAP1 is sufficient to induce invasive cervical cancer, implying that HPV is not necessary for cervical cancer development. However, HPV synergizes with YAP1 to drive the initiation and progression of cervical carcinogenesis. YAP1, via upregulating the putative HPV receptor molecules and suppressing host cell innate immunity, facilitates HPV infection (and potentially the establishment of persistent HPV infection). HPV oncoproteins, in turn, suppress the Hippo pathway and stabilize YAP1 protein to promote the oncogenic action of YAP1. Although HPV alone is insufficient to induce cervical cancer, it is worth noting that a combination of HPV and high-level of 17β-estradiol is able to induce the development of cervical cancer.^6,7