CXCL-12/stromal cell-derived factor-1 alpha transactivates HER2-neu in breast cancer cells by a novel pathway involving Src kinase activation

Cabioglu N., Summy J., Miller C., Parikh N., Sahin A., Tuzlali S., ...Daha Fazla

CANCER RESEARCH, cilt.65, ss.6493-6497, 2005 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 65 Konu: 15
  • Basım Tarihi: 2005
  • Doi Numarası: 10.1158/0008-5472.can-04-1303
  • Sayfa Sayıları: ss.6493-6497


Experimental evidence suggests that CXCR4, a G(i) protein-coupled receptor for the ligand CXCL12/stromal cell-derived factor-lot (SDF-1 alpha), plays a role in breast cancer metastasis. Transactivation of HER2-neu by G protein-coupled receptor activation has been reported as a ligand-independent mechanism of activating tyrosine kinase receptors. We found that SDF-1 alpha transactivated HER2-neu in the breast cancer cell lines MDA-MB-361 and SKBR3, which express both CXCR4 and HER2-neu. AMD3100, a CXCR4 inhibitor, PKI 166, an epidermal growth factor receptor/HER2-neu tyrosine kinase inhibitor, and PP2, a Src kinase inhibitor, each blocked SM-1 alpha-induced HER2-neu phosphorylation. Blocking Src kinase, with PP2 or using a kinase-inactive Src construct, and inhibiting epidermal growth factor receptor/HER2-neu signaling with PKI 166 each inhibited SDF-1 alpha-stimulated cell migration. We report a novel mechanism of HER2-neu transactivation through SDF-1 alpha stimulation of CXCR4 that involves Src kinase activation.