Chiu Connie G, St-Pierre Pascal, Nabi Ivan R, Wiseman Sam M
St Paul's Hospital, Department of Surgery, University of British Columbia, C303-1081 Burrard Street, Vancouver, BC, Canada.
Expert Rev Anticancer Ther. 2008 Feb;8(2):207-17. doi: 10.1586/14737140.8.2.207.
The ability to target and alter the metastatic activity of cancer cells is a key avenue for cancer therapeutics. While local tumor control is often achieved through surgical resection, patient morbidity and mortality is dependent upon the control of regional and distant spread of disease. Autocrine motility factor receptor (AMFR) is an internalizing cell surface receptor that also exhibits ubiquitin E3 ligase activity in the endoplasmic reticulum. Stimulation of AMFR by its ligand (autocrine motility factor/phosphoglucose isomerase) alters cellular adhesion, proliferation, motility, and apoptosis. Increased AMFR expression has been reported in numerous human cancer types. Review of these studies suggests that AMFR upregulation is significantly correlated with more advanced tumor stage and decreased survival for cancer of the lung, esophagus, stomach, colon, rectum, liver and skin. AMFR has also served as an independent predictor of poor disease prognosis in these tumor types. Significant associations between AMFR expression and other clinicopathologic parameters implicated in disease progression have also been reported. Further characterization of AMFR in human cancer and the development of an understanding of the molecular regulation of this protein is critical for its future role as a target for anticancer agents.
靶向并改变癌细胞转移活性的能力是癌症治疗的关键途径。虽然局部肿瘤控制通常可通过手术切除实现，但患者的发病率和死亡率取决于对疾病局部和远处扩散的控制。自分泌运动因子受体（AMFR）是一种内化细胞表面受体，在内质网中也表现出泛素E3连接酶活性。其配体（自分泌运动因子/磷酸葡萄糖异构酶）对AMFR的刺激会改变细胞黏附、增殖、运动和凋亡。在多种人类癌症类型中均报道了AMFR表达增加。对这些研究的综述表明，AMFR上调与更晚期的肿瘤分期显著相关，且与肺癌、食管癌、胃癌、结肠癌、直肠癌、肝癌和皮肤癌患者的生存率降低相关。在这些肿瘤类型中，AMFR也已成为疾病预后不良的独立预测指标。还报道了AMFR表达与疾病进展中涉及的其他临床病理参数之间存在显著关联。进一步明确AMFR在人类癌症中的特征，并深入了解该蛋白的分子调控机制，对于其未来作为抗癌药物靶点的作用至关重要。
