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Novel roles of NHE1 in motility of serum‐starved MCF7 breast cancer cells expressing constitutively active ErbB2
Author(s) -
Pedersen Stine Falsig,
Lauritzen Gitte,
Gorbatenko Andrej,
Lund Stine F.,
Dybboe Rie,
Schwab Albrecht,
Stock ChristianMartin
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.656.2
The Na + /H + exchanger NHE1 has been implicated in control of cell motility, yet the mechanisms involved and the roles of other acid‐extruding transporters are incompletely understood. Here, we address the roles of NHE1 and the Na + ,HCO 3 − cotransporter NBCn1 in motility of MCF7 breast cancer cells expressing a constitutively active ErbB2 receptor (ΔNErbB2). Cells were serum‐starved to partially simulate the tumor microenvironment. ΔNErbB2 expression was associated with increased activities of ERK1/2, p90RSK and Akt, upregulation of NBCn1, Ser703‐phosphorylation of NHE1, and NHE1‐inhibitor (EIPA)‐sensitive pericellular acidification. Adhesion and migration on collagen I were augmented by ΔNErbB2 expression. Surprisingly, both processes were further stimulated by EIPA, unaffected by the NBC inhibitor S0895 and inhibited by ~50% by the RSK inhibitor SL0101. Invasion through collagen I and basal lamina was unaffected or augmented by EIPA in a complex manner dependent on serum and ΔNErbB2. In conclusion, in serum‐starved ΔNErbB2‐expressing MCF‐7 cells, NHE1 may play a negative rather than stimulatory role in cell motility. Financial support: Novo Nordisk Foundation, Danish Cancer Society, Danish National Research Council.