Nabi I R, Watanabe H, Raz A
Cancer Metastasis Program, Michigan Cancer Foundation, Detroit.
Cancer Metastasis Rev. 1992 Mar;11(1):5-20. doi: 10.1007/BF00047599.
The ability to locomote and migrate is fundamental to the acquisition of invasive and metastatic properties by tumor cells. Autocrine motility factor (AMF) is a 55 kD cytokine produced by various tumor cells which stimulates their in vitro motility and in vivo lung colonizing ability. AMF stimulates cell motility via a receptor-mediated signalling pathway. Signal transduction following binding of AMF to its receptor, a cell surface glycoprotein of 78 kD (gp78) homologous to p53, is mediated by a pertussis toxin sensitive G protein, inositol phosphate production and the phosphorylation of gp78. Cell surface gp78 is localized to the leading and trailing edges of motile cells but following cell permeabilization is found within an extended network of intracellular tubulovesicles. Gp78 tubulovesicles colocalize with microtubules and extension of the tubulovesicular network to the cell periphery is dependent on the presence of intact microtubules. Gp78 labeled vesicles can be induced to translocate between the cell center and periphery by altering intracellular pH as previously described for tubulovesicles labeled by fluid phase uptake. Anti-gp78 mAb added to viable motile cells is localized to large multivesicular bodies which, with time, relocate to the leading edge. Binding of AMF to its receptor induces signal transduction, similar to chemotactic stimulation of neutrophil mobility, as well as the internalization and transport of its receptor to the leading edge stimulating pseudopodial protrusion and cell motility.
运动和迁移能力是肿瘤细胞获得侵袭和转移特性的基础。自分泌运动因子（AMF）是一种由多种肿瘤细胞产生的55kD细胞因子，可刺激其体外运动能力和体内肺定植能力。AMF通过受体介导的信号通路刺激细胞运动。AMF与其受体（一种与p53同源的78kD细胞表面糖蛋白gp78）结合后的信号转导由百日咳毒素敏感的G蛋白、肌醇磷酸生成和gp78的磷酸化介导。细胞表面gp78定位于运动细胞的前缘和后缘，但在细胞通透后，可在细胞内微管泡的扩展网络中发现。Gp78微管泡与微管共定位，微管泡网络向细胞周边的延伸依赖于完整微管的存在。如先前对通过液相摄取标记的微管泡所描述的那样，通过改变细胞内pH值，可诱导Gp78标记的囊泡在细胞中心和周边之间转运。添加到活的运动细胞中的抗gp78单克隆抗体定位于大型多囊泡体，随着时间的推移，这些多囊泡体会重新定位到前缘。AMF与其受体的结合诱导信号转导，类似于对中性粒细胞迁移的趋化刺激，以及其受体的内化和转运至前缘，刺激伪足突出和细胞运动。
