PMID- 25261255 OWN - NLM STAT- MEDLINE DCOM- 20150122 LR - 20161125 IS - 1873-3468 (Electronic) IS - 0014-5793 (Linking) VI - 588 IP - 21 DP - 2014 Nov 3 TI - Amphiregulin induces human ovarian cancer cell invasion by down-regulating E-cadherin expression. PG - 3998-4007 LID - S0014-5793(14)00693-0 [pii] LID - 10.1016/j.febslet.2014.09.017 [doi] AB - Aberrant epidermal growth factor receptor (EGFR) activation is associated with ovarian cancer progression. In this study, we report that the EGFR ligand amphiregulin (AREG) stimulates cell invasion and down-regulates E-cadherin expression in two human ovarian cancer cell lines, SKOV3 and OVCAR5. In addition, AREG increases the expression of transcriptional repressors of E-cadherin including SNAIL, SLUG and ZEB1. siRNA targeting SNAIL or SLUG abolishes AREG-induced cell invasion. Moreover, ERK1/2 and AKT pathways are involved in AREG-induced E-cadherin down-regulation and cell invasion. Finally, we show that three EGFR ligands, AREG, epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha), exhibit comparable effects in down-regulating E-cadherin and promoting cell invasion. This study demonstrates that AREG induces ovarian cancer cell invasion by down-regulating E-cadherin expression. CI - Copyright (c) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. FAU - So, Wai-Kin AU - So WK AD - Department of Obstetrics and Gynecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada. FAU - Fan, Qianlan AU - Fan Q AD - Department of Obstetrics and Gynecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada. FAU - Lau, Man-Tat AU - Lau MT AD - Department of Obstetrics and Gynecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada. FAU - Qiu, Xin AU - Qiu X AD - Department of Obstetrics and Gynecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada. FAU - Cheng, Jung-Chien AU - Cheng JC AD - Department of Obstetrics and Gynecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada. FAU - Leung, Peter C K AU - Leung PC AD - Department of Obstetrics and Gynecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada. Electronic address: peter.leung@ubc.ca. LA - eng GR - Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140923 PL - England TA - FEBS Lett JT - FEBS letters JID - 0155157 RN - 0 (Amphiregulin) RN - 0 (Cadherins) RN - 0 (SNAI1 protein, human) RN - 0 (Snail Family Transcription Factors) RN - 0 (Transcription Factors) RN - 0 (Transforming Growth Factor alpha) RN - 62229-50-9 (Epidermal Growth Factor) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Amphiregulin/deficiency/genetics/*pharmacology MH - Cadherins/*genetics MH - Cell Line, Tumor MH - Down-Regulation/*drug effects MH - Epidermal Growth Factor/pharmacology MH - Female MH - Gene Knockdown Techniques MH - Humans MH - MAP Kinase Signaling System/drug effects MH - Neoplasm Invasiveness MH - Ovarian Neoplasms/*pathology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Snail Family Transcription Factors MH - Transcription Factors/deficiency/genetics/metabolism MH - Transforming Growth Factor alpha/pharmacology OTO - NOTNLM OT - Amphiregulin OT - E-cadherin OT - Invasion OT - Ovarian cancer EDAT- 2014/09/28 06:00 MHDA- 2015/01/23 06:00 CRDT- 2014/09/28 06:00 PHST- 2014/07/24 00:00 [received] PHST- 2014/09/05 00:00 [revised] PHST- 2014/09/11 00:00 [accepted] PHST- 2014/09/28 06:00 [entrez] PHST- 2014/09/28 06:00 [pubmed] PHST- 2015/01/23 06:00 [medline] AID - S0014-5793(14)00693-0 [pii] AID - 10.1016/j.febslet.2014.09.017 [doi] PST - ppublish SO - FEBS Lett. 2014 Nov 3;588(21):3998-4007. doi: 10.1016/j.febslet.2014.09.017. Epub 2014 Sep 23.