Heregulin-β1 promotes metastasis of breast cancer cell line SKBR3 through upregulation of Snail and induction of epithelial-mesenchymal transition

被引：27

作者：

Cheng, LianSheng ^{[1
]}

Zha, Zhao ^{[1
]}

Lang, Bo ^{[1
]}

Liu, Jing ^{[1
]}

Yao, XueBiao ^{[1
]}

机构：

[1] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Peoples R China

来源：

CANCER LETTERS | 2009年 / 280卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Heregulin-beta; 1; EMT; Snail; HER3; Akt; EPIDERMAL GROWTH-FACTOR; GENE-EXPRESSION; DIFFERENTIATION FACTOR; TUMOR PROGRESSION; PROTEIN-KINASE; ROLES; TRANSFORMATION; MIGRATION; SURVIVAL; MOTILITY;

D O I：

10.1016/j.canlet.2009.02.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

HRG-beta 1 stimulation of breast cancer cell line SKBR3 resulted in not only increased cell migration and invasion, upregulation of some mesenchymal markers, and downregulation of epithelial marker, but also upregulation of transcription factor Snail and its nuclear translocation. Similar results were acquired for cells transfected with Snail cDNA. Furthermore, downregulation of Snail by siRNA attenuated HRG-beta 1 induced EMT-like phenotype. Inhibition of Akt kinase activation by a PI3K inhibitor LY294002, or exogenous expression of a kinase-dead mutant of Akt abrogated the increase of Snail expression induced by HRG-beta 1. Conversely, expression of a constitutively active Akt resulted in increase of Snail expression. These results indicated that Snail upregulation by HRG-beta 1 is mediated via the PI3K/Akt signaling pathway and that Snail plays a key role in HRG-beta 1 induced breast cancer cell metastasis through induction of EMT. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

引用

页码：50 / 60

页数：11

共 40 条

[1]

Heregulin regulates cytoskeletal reorganization and cell migration through the p21-activated kinase-1 via phosphatidylinositol-3 kinase [J].