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The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to
regulate cervical cancer progression
#MMPMID26417066
He C
; Mao D
; Hua G
; Lv X
; Chen X
; Angeletti PC
; Dong J
; Remmenga SW
; Rodabaugh KJ
; Zhou J
; Lambert PF
; Yang P
; Davis JS
; Wang C
EMBO Mol Med
2015[Nov]; 7
(11
): 1426-49
PMID26417066
show ga
The Hippo signaling pathway controls organ size and tumorigenesis through a
kinase cascade that inactivates Yes-associated protein (YAP). Here, we show that
YAP plays a central role in controlling the progression of cervical cancer. Our
results suggest that YAP expression is associated with a poor prognosis for
cervical cancer. TGF-? and amphiregulin (AREG), via EGFR, inhibit the Hippo
signaling pathway and activate YAP to induce cervical cancer cell proliferation
and migration. Activated YAP allows for up-regulation of TGF-?, AREG, and EGFR,
forming a positive signaling loop to drive cervical cancer cell proliferation.
HPV E6 protein, a major etiological molecule of cervical cancer, maintains high
YAP protein levels in cervical cancer cells by preventing proteasome-dependent
YAP degradation to drive cervical cancer cell proliferation. Results from human
cervical cancer genomic databases and an accepted transgenic mouse model strongly
support the clinical relevance of the discovered feed-forward signaling loop. 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.
|*Signal Transduction
[MESH]
|Adaptor Proteins, Signal Transducing/*metabolism
[MESH]
free
free
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