YAP forms autocrine loops with the ERBB pathway to regulate ovarian cancer initiation and progression View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Chunbo He, Xiangmin Lv, Guohua Hua, Subodh M Lele, Steven Remmenga, Jixin Dong, John S Davis, Cheng Wang

ABSTRACT

Mechanisms underlying ovarian cancer initiation and progression are unclear. Herein, we report that the Yes-associated protein (YAP), a major effector of the Hippo tumor suppressor pathway, interacts with ERBB signaling pathways to regulate the initiation and progression of ovarian cancer. Immunohistochemistry studies indicate that YAP expression is associated with poor clinical outcomes in patients. Overexpression or constitutive activation of YAP leads to transformation and tumorigenesis in human ovarian surface epithelial cells, and promotes growth of cancer cells in vivo and in vitro. YAP induces the expression of epidermal growth factor (EGF) receptors (EGFR, ERBB3) and production of EGF-like ligands (HBEGF, NRG1 and NRG2). HBEGF or NRG1, in turn, activates YAP and stimulates cancer cell growth. Knockdown of ERBB3 or HBEGF eliminates YAP effects on cell growth and transformation, whereas knockdown of YAP abrogates NRG1- and HBEGF-stimulated cell proliferation. Collectively, our study demonstrates the existence of HBEGF & NRGs/ERBBs/YAP/HBEGF & NRGs autocrine loop that controls ovarian cell tumorigenesis and cancer progression. More... »

PAGES

6040-6054

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/onc.2015.52

DOI

http://dx.doi.org/10.1038/onc.2015.52

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052774966

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25798835


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