Journal of cellular physiology
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The cellular function of electroneutral K-Cl cotransport (KCC) is to regulate epithelial ion transport and osmotic homeostasis. Here we investigate the mechanisms by which insulin-like growth factor 1 (IGF-1) cooperates with KCC to modulate breast cancer biology. IGF-1 stimulates KCC activity of MCF-7 breast cancer cells in a dose- and time-dependent manner. ⋯ The expression level of IGF-1 and KCC polypeptides in the surgical specimens showed a good linear correlation, suggesting autocrine or paracrine IGF-1 stimulation of KCC production in vivo. Among patients with early-stage node-negative breast cancer, disease-free survival (DFS) and overall survival (OS) curves were significantly different based on IGF-1 and KCC expression. Thus, we conclude that KCC activation by IGF-1 plays an important role in IGF-1 receptor signaling to promote growth and spread of breast cancer cells.