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

Gitte Lauritzen; Christian-Martin Stock; Justine Lemaire; Stine F. Lund; Mie Frid Jensen; Britt Damsgaard; Katrine Seide Petersen; Maria Wiwel; Lone Rønnov-Jessen; Albrecht Schwab; Stine Helene Falsig Pedersen

doi:10.1016/j.canlet.2011.11.023

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

Gitte Lauritzen, Christian-Martin Stock, Justine Lemaire, Stine F. Lund, Mie Frid Jensen, Britt Damsgaard, Katrine Seide Petersen, Maria Wiwel, Lone Rønnov-Jessen, Albrecht Schwab, Stine Helene Falsig Pedersen

Cell Biology and Physiology

69 Citations (Scopus)

Abstract

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 (ΔNErbB2). ΔNErbB2 expression elicited NBCn1 upregulation, Ser ⁷⁰³-phosphorylation of NHE1, and NHE1-inhibitor (EIPA)-sensitive pericellular acidification, in conjunction with increased expression of β1 integrin and ERM proteins. Active ERM proteins and NHE1 colocalized strongly to invadopodial rosettes, the diameter of which was increased by ΔNErbB2. Adhesion and migration on collagen-I were augmented by ΔNErbB2, 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.

Original language	English
Journal	Cancer Letters
Volume	317
Issue number	2
Pages (from-to)	172-183
Number of pages	12
ISSN	0304-3835
DOIs	https://doi.org/10.1016/j.canlet.2011.11.023
Publication status	Published - 28 Apr 2012

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10.1016/j.canlet.2011.11.023

The Na+/H+ exchanger NHE1, but not the Na+, HCO3- cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2Final published version, 1.67 MB

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Lauritzen, G., Stock, C-M., Lemaire, J., Lund, S. F., Jensen, M. F., Damsgaard, B., Petersen, K. S., Wiwel, M., Rønnov-Jessen, L., Schwab, A., & Pedersen, S. H. F. (2012). The Na⁺/H⁺ exchanger NHE1, but not the Na⁺, HCO₃^- cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2. Cancer Letters, 317(2), 172-183. https://doi.org/10.1016/j.canlet.2011.11.023

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 et al.

In: Cancer Letters, Vol. 317, No. 2, 28.04.2012, p. 172-183.

Research output: Contribution to journal › Journal article › Research › peer-review

Lauritzen, G, Stock, C-M, Lemaire, J, Lund, SF, Jensen, MF, Damsgaard, B, Petersen, KS, Wiwel, M, Rønnov-Jessen, L, Schwab, A & Pedersen, SHF 2012, 'The Na⁺/H⁺ exchanger NHE1, but not the Na⁺, HCO₃^- cotransporter NBCn1, regulates motility of MCF7 breast cancer cells expressing constitutively active ErbB2', Cancer Letters, vol. 317, no. 2, pp. 172-183. https://doi.org/10.1016/j.canlet.2011.11.023

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abstract = "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 (ΔNErbB2). ΔNErbB2 expression elicited NBCn1 upregulation, Ser 703-phosphorylation of NHE1, and NHE1-inhibitor (EIPA)-sensitive pericellular acidification, in conjunction with increased expression of β1 integrin and ERM proteins. Active ERM proteins and NHE1 colocalized strongly to invadopodial rosettes, the diameter of which was increased by ΔNErbB2. Adhesion and migration on collagen-I were augmented by ΔNErbB2, 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.",

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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

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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 +, HCO3- cotransporter NBCn1 in motility of serum-starved MCF-7 breast cancer cells expressing constitutively active ErbB2 (ΔNErbB2). ΔNErbB2 expression elicited NBCn1 upregulation, Ser 703-phosphorylation of NHE1, and NHE1-inhibitor (EIPA)-sensitive pericellular acidification, in conjunction with increased expression of β1 integrin and ERM proteins. Active ERM proteins and NHE1 colocalized strongly to invadopodial rosettes, the diameter of which was increased by ΔNErbB2. Adhesion and migration on collagen-I were augmented by ΔNErbB2, 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 +, HCO3- cotransporter NBCn1 in motility of serum-starved MCF-7 breast cancer cells expressing constitutively active ErbB2 (ΔNErbB2). ΔNErbB2 expression elicited NBCn1 upregulation, Ser 703-phosphorylation of NHE1, and NHE1-inhibitor (EIPA)-sensitive pericellular acidification, in conjunction with increased expression of β1 integrin and ERM proteins. Active ERM proteins and NHE1 colocalized strongly to invadopodial rosettes, the diameter of which was increased by ΔNErbB2. Adhesion and migration on collagen-I were augmented by ΔNErbB2, 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.

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