title: Sprouty4 mediates amphiregulin-induced down-regulation of E-cadherin and cell invasion in human ovarian cancer cells.
abstract: Sprouty (SPRY) proteins are well-characterized factors that inhibit receptor tyrosine kinase (RTK)-mediated activation of cellular signaling pathways. The down-regulation of SPRY4 expression has been reported in human ovarian cancer. However, the specific roles and mechanisms by which SPRY4 affects ovarian cancer progression are completely unknown. Amphiregulin (AREG) binds exclusively to the epidermal growth factor receptor (EGFR) and has been considered to be a dominant autocrine/paracrine EGFR ligand in ovarian cancer. In the present study, we first examined the effects of AREG on SPRY4 expression and the possible underlying molecular mechanisms involved in this process in two human ovarian cancer cell lines. Our results demonstrated that treatment with AREG up-regulated SPRY4 expression by activating the ERK1/2 signaling pathway. In addition, we showed that small interfering RNA (siRNA)-mediated knockdown of SPRY4 attenuated the AREG-induced down-regulation of E-cadherin by inhibiting the expression of SNAIL but not SLUG. In contrast, overexpression of SPRY4 enhanced AREG-induced down-regulation of E-cadherin by increasing the expression of SNAIL. Moreover, SPRY4 knockdown attenuated AREG-induced cell migration and invasion. Overexpression of SPRY4 enhanced AREG-induced cell invasion. This study reveals that SPRY4 is involved in EGFR-mediated human ovarian cancer progression.
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Room 317, 950 west 28th Ave, Vancouver, BC, V5Z 4H4, Canada.
authors.forename: Wai-Kin
authors.initials: WK
authors.lastname: So
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Room 317, 950 west 28th Ave, Vancouver, BC, V5Z 4H4, Canada.
authors.forename: Jung-Chien
authors.initials: JC
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Room 317, 950 west 28th Ave, Vancouver, BC, V5Z 4H4, Canada.|Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China, 200011.
authors.forename: Yingtao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China, 200011.
authors.forename: Congjian
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Room 317, 950 west 28th Ave, Vancouver, BC, V5Z 4H4, Canada.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Room 317, 950 west 28th Ave, Vancouver, BC, V5Z 4H4, Canada.
authors.forename: Vincent T W
authors.initials: VT
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Room 317, 950 west 28th Ave, Vancouver, BC, V5Z 4H4, Canada. peter.leung@ubc.ca.
authors.forename: Peter C K
authors.initials: PC
authors.lastname: Leung
mesh_terms: D066258:Amphiregulin / Q000494:pharmacology*; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D066258:Amphiregulin; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C499038:SPRY4 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Amphiregulin; E-cadherin; Ovarian cancer; Sprouty4