The high level of XBP1 can promote its own activation under the hypoxia-associated ERS and UPR.22 Thus, the enhanced expression of XBP1 and stromal molecules CXCR4 and CD44 can be sufficient for initiating the pathway, triggering tumor APVT growth, and increasing tumor aggressiveness. The gene discussed is CXCR4; the disease is neoplasm.