Nerve growth factor (
NGF) is increasingly implicated in
cervical cancer progression, but its mechanism in
cervical cancer is unclear. Here, studies demonstrate that
NGF inhibits the Hippo signaling pathway and activates Yes-associated
protein (YAP) to induce
cervical cancer cell proliferation and migration. Our results suggested that stimulation of
NGF promoted cell growth and migration and activated YAP in HeLa and C-33A cell lines. The expression of YAP target genes (CTGF and ANKRD1) was upregulated after
NGF treatment. The
NGF inhibitor
Ro 08-2750 and
siRNA-mediated
NGF receptor gene silencing suppressed HeLa and C-33A cells proliferation and migration, activated large suppressor
kinase 1 (LATS1)
kinase activity, and suppressed YAP function. In addition, the expression of YAP target genes (CTGF and ANKRD1) was suppressed by
Ro 08-2750 treatment in HeLa and C-33A cells. Interestingly, proliferation was significantly higher in
NGF-treated cells than in control cells, and this effect was completely reversed by the YAP small molecule inhibitor-
verteporfin. Furthermore, the mouse xenograft model shows that
NGF regulates YAP oncogenic activity in vivo. Mechanistically,
NGF stimulation inactivates LATS1 and activates YAP, and
NGF inhibition was found to induce large suppressor
kinase 1 (LATS1) phosphorylation. Taken together, these data provide the first direct evidence of crosstalk between the
NGF signaling and Hippo
cancer pathways, an interaction that affects
cervical cancer progression. Our study indicates that combined targeting of the
NGF signaling and the Hippo pathway represents a novel therapeutic strategy for treatment of
cervical cancer.