Following activation,there is lack of desensitization , enhanced calcium mobilization ,and a decrease in SDF promoted internalization
2-Cancer The expression of CXCR4 has been detected in 23 different cancers of various origins and is the most common chemokine receptor expressed on cancer cells. O2 Activation (HIF1) Hypoxia inducible factor 1 CXCR4 (VHL)von hipple lindau Breast cancer VEGF metastasis NF- k B Enhanced migration and adhision of rhabdomyosarcoma Oncoprotein PAX-FKHR Enhanced the transforming ability of breast cancer cells Oncoprotein RET/PCT
Involvement of CXCR4/SDF-1 system in cancer progression Pancreatic cancer Kosshiba et al., Clin. Cancer Res. 2000 Neuroblastoma Geminder et al., J. Immunol. 2001 Breast cancer Muller et al., Nature 2001 Rhabdomyosarcoma Libura et al., Blood 2002 Prostate cancer Taichman et al., Cancer Res. 2002 Colon cancer Zeelemberg et al., Cancer Res. 2003 Osteosarcoma Perissinotto et al., Clin Cancer Res. 2005 Laverdiere et al., Clin Cancer Res. 2005 N on-small cell lung cancer cells Su et al., Clin Cancer Res. 2005 E sophageal cancer Kaifi et al., J Natl Cancer Inst. 2005 Carcinomatosis of Gastric Cancer Yasumoto et al., Cancer Res. 2006 G lioma Ehtesham et al., Oncogene 2006 Melanoma Bartolome et al., Cancer Res. 2006
Cancer cell Y Y chemokine receptor chemokine endothelium Target tissue Non-target tissue Cancer cell Y Y endothelium different chemokine
The C-tail is absolutely critical for proper regulation of CXCR4
It is expected that the functional consequense of CXCR4 expression on cancer cells would be varied based on the numerous roles of the CXCR4-SDF signaling axie.for example,the combination of CXCR4 expression and interaction with stormal or nurse-like cells in chronic lymphocytic leukemia and multiple myeloma may account for resistence to spontaneous/drug induced apoptosis and cell adhesion-mediated drug resistance,essentially providing a protective niche.