The Na+/H+ exchanger NHE1, but not the Na+, HCO3- cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2

被引：86

作者：

Lauritzen, Gitte ^{[1
]}

Stock, Christian-Martin ^{[2
]}

Lemaire, Justine ^{[1
]}

Lund, Stine F. ^{[1
]}

Jensen, Mie Frid ^{[1
]}

Damsgaard, Britt ^{[1
]}

Petersen, Katrine Seide ^{[1
]}

Wiwel, Maria ^{[1
]}

Ronnov-Jessen, Lone ^{[1
]}

Schwab, Albrecht ^{[2
]}

Pedersen, Stine Falsig ^{[1
]}

机构：

[1] Univ Copenhagen, Dept Biol, Sect Cell & Dev Biol, DK-2100 Copenhagen, Denmark

[2] Univ Munster, Inst Physiol 2, D-48149 Munster, Germany

来源：

CANCER LETTERS | 2012年 / 317卷 / 02期

关键词：

Motility; Cytoskeleton; Signaling; Adhesion; HER2; pH-regulation; PH NANOENVIRONMENT; MELANOMA-CELLS; ERM PROTEINS; SURFACE PH; INTEGRIN; ADHESION; PHOSPHORYLATION; ACTIVATION; MIGRATION; MEMBRANE;

D O I：

10.1016/j.canlet.2011.11.023

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We and others have shown central roles of the Na+/H+ exchanger NHE1 in cell motility. The aim of this study was to determine the roles of NHE1 and of the Na+, HCO3- cotransporter NBCn1 in motility of serum-starved MCF-7 breast cancer cells expressing constitutively active ErbB2 (Delta NErbB2). Delta NErbB2 expression elicited NBCn1 upregulation, Ser(703)-phosphorylation of NHE1, and NHE1-inhibitor (EIPA)-sensitive pericellular acidification, in conjunction with increased expression of beta 1 integrin and ERM proteins. Active ERM proteins and NHE1 colocalized strongly to invadopodial rosettes, the diameter of which was increased by Delta NErbB2. Adhesion and migration on collagen-1 were augmented by Delta NErbB2, unaffected by the NBC inhibitor S0859, and further stimulated by EIPA in a manner potentiated by PI3K-Akt-inhibidon. These findings demonstrate that NHE1 inhibition can enhance cancer cell motility, adding an important facet to the understanding of NHE1 in cancer. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

引用

页码：172 / 183

页数：12

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