双调蛋白通过下调E-钙黏蛋白的表达诱导人卵巢癌细胞侵袭。
Amphiregulin induces human ovarian cancer cell invasion by down-regulating E-cadherin expression.
作者信息
So Wai-Kin, Fan Qianlan, Lau Man-Tat, Qiu Xin, Cheng Jung-Chien, Leung Peter C K
机构信息
Department of Obstetrics and Gynecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
Department of Obstetrics and Gynecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
出版信息
FEBS Lett. 2014 Nov 3;588(21):3998-4007. doi: 10.1016/j.febslet.2014.09.017. Epub 2014 Sep 23.
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-α (TGF-α), 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.
异常的表皮生长因子受体（EGFR）激活与卵巢癌进展相关。在本研究中，我们报告表皮生长因子受体配体双调蛋白（AREG）可刺激两种人卵巢癌细胞系SKOV3和OVCAR5的细胞侵袭并下调E-钙黏蛋白的表达。此外，AREG增加E-钙黏蛋白转录抑制因子的表达，包括SNAIL、SLUG和ZEB1。靶向SNAIL或SLUG的小干扰RNA（siRNA）可消除AREG诱导的细胞侵袭。此外，细胞外信号调节激酶1/2（ERK1/2）和蛋白激酶B（AKT）信号通路参与AREG诱导的E-钙黏蛋白下调和细胞侵袭。最后，我们表明三种表皮生长因子受体配体，即AREG、表皮生长因子（EGF）和转化生长因子-α（TGF-α），在下调E-钙黏蛋白和促进细胞侵袭方面具有相似的作用。本研究表明，AREG通过下调E-钙黏蛋白表达诱导卵巢癌细胞侵袭。
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