The Na+/H+ exchanger NHE1, but not the Na+, HCO3- cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2
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The Na+/H+ exchanger NHE1, but not the Na+, HCO3- cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2. / Lauritzen, Gitte; Stock, Christian-Martin; Lemaire, Justine; Lund, Stine F.; Jensen, Mie Frid; Damsgaard, Britt; Petersen, Katrine Seide; Wiwel, Maria; Rønnov-Jessen, Lone; Schwab, Albrecht; Pedersen, Stine Helene Falsig.
In: Cancer Letters, Vol. 317, No. 2, 2012, p. 172-183.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The Na+/H+ exchanger NHE1, but not the Na+, HCO3- cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2
AU - Lauritzen, Gitte
AU - Stock, Christian-Martin
AU - Lemaire, Justine
AU - Lund, Stine F.
AU - Jensen, Mie Frid
AU - Damsgaard, Britt
AU - Petersen, Katrine Seide
AU - Wiwel, Maria
AU - Rønnov-Jessen, Lone
AU - Schwab, Albrecht
AU - Pedersen, Stine Helene Falsig
N1 - Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
PY - 2012
Y1 - 2012
N2 - 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(+), HCO(3)(-) cotransporter NBCn1 in motility of serum-starved MCF-7 breast cancer cells expressing constitutively active ErbB2 (¿NErbB2). ¿NErbB2 expression elicited NBCn1 upregulation, Ser(703)-phosphorylation of NHE1, and NHE1-inhibitor (EIPA)-sensitive pericellular acidification, in conjunction with increased expression of ß1 integrin and ERM proteins. Active ERM proteins and NHE1 colocalized strongly to invadopodial rosettes, the diameter of which was increased by ¿NErbB2. Adhesion and migration on collagen-I were augmented by ¿NErbB2, unaffected by the NBC inhibitor S0859, and further stimulated by EIPA in a manner potentiated by PI3K-Akt-inhibition. These findings demonstrate that NHE1 inhibition can enhance cancer cell motility, adding an important facet to the understanding of NHE1 in cancer.
AB - 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(+), HCO(3)(-) cotransporter NBCn1 in motility of serum-starved MCF-7 breast cancer cells expressing constitutively active ErbB2 (¿NErbB2). ¿NErbB2 expression elicited NBCn1 upregulation, Ser(703)-phosphorylation of NHE1, and NHE1-inhibitor (EIPA)-sensitive pericellular acidification, in conjunction with increased expression of ß1 integrin and ERM proteins. Active ERM proteins and NHE1 colocalized strongly to invadopodial rosettes, the diameter of which was increased by ¿NErbB2. Adhesion and migration on collagen-I were augmented by ¿NErbB2, unaffected by the NBC inhibitor S0859, and further stimulated by EIPA in a manner potentiated by PI3K-Akt-inhibition. These findings demonstrate that NHE1 inhibition can enhance cancer cell motility, adding an important facet to the understanding of NHE1 in cancer.
U2 - 10.1016/j.canlet.2011.11.023
DO - 10.1016/j.canlet.2011.11.023
M3 - Journal article
C2 - 22120673
VL - 317
SP - 172
EP - 183
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 2
ER -
ID: 37624261