The synergistic effects of CXCR4 and EGFR on promoting EGF-mediated metastasis in ovarian cancer cells.
CXC chemokine receptor 4 (CXCR4) is a cell surface receptor that has been reported to mediate the metastasis of many solid tumors including ovarian, breast, lung and prostate. The over-expression of the epidermal growth factor receptor (EGFR) is associated with the majority of ovarian cancer and has been implicated in the process of malignant transformation by promoting cell proliferation, survival, and motility. In this research, the result first showed that epidermis growth factor (EGF) enhanced the expression of CXCR4 and the migration of ovarian cancer cells, moreover, both stromal cell derived factor-1alpha (SDF-1alpha) and EGF-induced high matrix metallopeptidase 9 (MMP9) expressions. Molecular analysis indicated that augmented CXCR4 and MMP9 expression was regulated by phosphatidylinositol-3-kinase(PI3K)/Akt signal transduction pathway. These results suggested a possible important "cross-talk" between CXCR4 and EGFR intracellular pathways that might link signals of tumor deteriorated and provided a plausible explanation for the poor overall survival rate of patients whose co-expression of CXCR4 and EGFR was detected in their tissue sections. It enlightened that, compared to the respective inhibition of the EGFR or CXCR4 signaling, the simultaneous inhibition of them might be a more useful therapeutic strategy of cancer.
Guo
Zhigang
Z
College of Bioengineering, Key Laboratory for Biomechanics and Tissue Engineering of the State Ministry of Education, Chongqing University, Chongqing 400044, PR China.
Cai
Shaoxi
S
Fang
Rui
R
Chen
Hongyuan
H
Du
Jun
J
Tan
Yi
Y
Ma
Weifeng
W
Hu
Houwen
H
Cai
Shaohui
S
Liu
Yiyao
Y
D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000502:physiology*; D066246:ErbB Receptors / Q000502:physiology*; D005260:Female; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D019718:Receptors, CXCR4; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9