Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis.
The receptor tyrosine kinase HER2 enhances tumor metastasis; however, its role in homing to metastatic organs is poorly understood. The chemokine receptor CXCR4 has recently been shown to mediate the movement of malignant cancer cells to specific organs. Here, we show that HER2 enhances the expression of CXCR4, which is required for HER2-mediated invasion in vitro and lung metastasis in vivo. HER2 also inhibits ligand-induced CXCR4 degradation. Finally, a significant correlation between HER2 and CXCR4 expression was observed in human breast tumor tissues, and CXCR4 expression correlated with a poor overall survival rate in patients with breast cancer. These results provide a plausible mechanism for HER2-mediated breast tumor metastasis and establish a functional link between HER2 and CXCR4 signaling pathways.
Li
Yan M
YM
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Pan
Yong
Y
Wei
Yongkun
Y
Cheng
Xiaoyun
X
Zhou
Binhua P
BP
Tan
Ming
M
Zhou
Xiaoyan
X
Xia
Weiya
W
Hortobagyi
Gabriel N
GN
Yu
Dihua
D
Hung
Mien-Chie
MC
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008024:Ligands; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D041681:NIH 3T3 Cells; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D008024:Ligands; D018719:Erb-b2 Receptor Tyrosine Kinases; D019718:Receptors, CXCR4