RRC ID 36943
Author He C, Lv X, Hua G, Lele SM, Remmenga S, Dong J, Davis JS, Wang C.
Title YAP forms autocrine loops with the ERBB pathway to regulate ovarian cancer initiation and progression.
Journal Oncogene
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.
Volume 34(50)
Pages 6040-54
Published 2015-12-10
DOI 10.1038/onc.2015.52
PII onc201552
PMID 25798835
PMC PMC4580488
MeSH Adaptor Proteins, Signal Transducing / physiology* Animals Cell Line, Tumor Cell Proliferation Disease Progression ErbB Receptors / physiology Female Heparin-binding EGF-like Growth Factor / physiology Humans Mice Ovarian Neoplasms / etiology* Phosphoproteins / physiology* Prognosis Receptor, ErbB-3 / physiology* Signal Transduction* Transcription Factors
IF 7.971
Times Cited 48
Human and Animal Cells KGN(RCB1154)