title: YAP forms autocrine loops with the ERBB pathway to regulate ovarian cancer initiation and progression.
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.
authors: Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE, USA.|College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, Hubei province, P.R. China.
authors: C
authors: C
authors: He
authors: Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE, USA.
authors: X
authors: X
authors: Lv
authors: Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE, USA.|College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, Hubei province, P.R. China.
authors: G
authors: G
authors: Hua
authors: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
authors: S M
authors: SM
authors: Lele
authors: Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE, USA.|Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
authors: S
authors: S
authors: Remmenga
authors: Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
authors: J
authors: J
authors: Dong
authors: Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE, USA.|Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.|Omaha Veterans Affairs Medical Center, Omaha, NE, USA.
authors: J S
authors: JS
authors: Davis
authors: Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE, USA.|Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
authors: C
authors: C
authors: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D066246:ErbB Receptors / Q000502:physiology; D005260:Female; D066257:Heparin-binding EGF-like Growth Factor / Q000502:physiology; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000209:etiology*; D010750:Phosphoproteins / Q000502:physiology*; D011379:Prognosis; D020893:Receptor, ErbB-3 / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C581292:ERBB3 protein, human; D066246:ErbB Receptors; D020893:Receptor, ErbB-3