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Journal of Medical Oncology & Therapeutics | Volume 4
March 18-19, 2019 | London, UK
Oncology & Cancer Therapy
International Conference on
Novel mechanism of the cervical carcinogenesis
Cheng Wang
Harvard Medical School, USA
H
PV infections are common inhealthywomenbut only rarely
cause cervical cancer, suggesting that individual genetic
susceptibility may play a critical role in the establishment of
persistent HPV infection and development of cervical cancer.
We provide convincing
in vitro
and
in vivo
evidence showing
that disruption of the Hippo pathway and subsequent
hyperactivation of
YAP1
oncogene is a critical pathological event
that determines individual susceptibility to HPV infection and
cervical carcinogenesis. We found that hyperactivation of YAP1
in mouse cervical epitheliumwas sufficient to induce malignant
transformation of cervical epithelial cells and promote
development of invasive cervical cancer. Cervical epithelial cell-
specific HPV16 E6/E7 and YAP1 double knock-in mouse model
demonstrated that HPV synergized with hyperactivated YAP1 to
promote the initiation and progression of cervical cancer. Our
mechanistic studies indicated that hyperactivation of YAP1 in
cervical epithelial cells facilitated HPV infection via increasing
the putative HPV receptor molecules and disrupting the host
cell innate immunity. Our finding challenges the dogma that
HPV is a necessary agent for the development of cervical cancer,
uncovers a novel mechanism for the cervical carcinogenesis,
and provides new targets for developing strategies to improve
prevention and treatment of cervical cancer.
e:
cwang34@mgh.harvard.edu