Overexpression of multiple signaling impaired CXCR4 constructs suggests that intracellular presence of CXCR4 protein, but neither its surface presence nor CXCL12-CXCR4 mediated signals are essential in modulating DR5 expression and therapy (paclitaxel) resistance in cancer. The gene discussed is TNFRSF10B; the disease is cancer.