CXCR4
小结
CXCR4编码蛋白是基质衍生因子CXCL12特异的趋化因子受体，CXCL12是一种对淋巴细胞具有强效趋化活性的分子。CXCR4-CXCL12信号轴通过自分泌和旁分泌相互作用促进癌细胞增殖，存活，运动和耐药性。CXCR4在癌细胞中的表达与含有高水平的CXCL12的组织转移有关，如骨、肺、肝和淋巴结。CXCR4-CXCL12轴通过缺氧诱导CXCR4表达和募集内皮祖细胞到肿瘤的来诱导恶性肿瘤中的血管生成。CXCR4的胚系突变会引起了WHIM综合征，一种以中性粒细胞减少为特征的免疫缺陷病。CXCR4体细胞突变在人类癌症中并不常见，但CXCR4的高表达在许多癌症中是不良预后的标志物，包括乳腺癌，卵巢癌，黑素瘤和前列腺癌。
CXCR4 is a chemokine receptor specific to the stromal-derived factor CXCL12, a molecule with potent chemotactic activity for lymphocytes. Through autocrine and paracrine interactions, the CXCR4-CXCL12 signaling axis promotes cancer cell proliferation, survival, motility and drug resistance. Expression of CXCR4 in cancer cells has been linked to metastasis to tissues containing high levels of CXCL12, like the bone, lungs, liver and lymph nodes. The CXCR4-CXCL12 axis also induces angiogenesis in several malignancies through hypoxia-induced CXCR4 expression and recruitment of endothelial progenitor cells to tumors. Germline mutations in CXCR4, including activating C-terminal truncating mutations, cause WHIM syndrome, an immunodeficiency disorder characterized by neutropenia. Somatic alterations in CXCR4 are found in Waldenström macroglobulinemia, but are rare in other cancers; elevated expression of CXCR4 is a poor prognostic marker in many cancers, including breast, ovarian, melanoma and prostate cancers. Inhibitors of the CXCL4-CXCL12 axis are in several Phase I/II clinical trials for stem cell mobilization and HIV research; these inhibitors have not yet been evaluated in the context of cancer.