PHP14是目前发现的哺乳动物中唯一一个组氨酸磷酸酶。本实验室前期研究发现14kD组氨酸磷酸酶(PHP14)的高表达与细胞的浸润能力和肿瘤病人的淋巴结转移具有显著的相关性，但其生物学功能尚未阐明。本工作通过RT-PCR和Western blot比较PHP14基因沉默细胞系和对照细胞系相关基因和蛋白的表达，发现PHP14可能通过NF-κB和JNK信号通路对下游基因表达以及蛋白活性的调控来影响血管生成、肺癌的发生和转移。另外，通过蛋白质组学的方法，还发现一些细胞骨架调节蛋白的表达水平在PHP14基因沉默前后存在显著差异。进而对两种细胞进行了微丝的染色，发现沉默PHP14肺癌细胞的伪足显著减少，微丝不能成束。这与所观察到的沉默细胞体外运动和浸润能力的降低相符。最后，通过TAP方法寻找PHP14的相互作用蛋白，获得了若干可能与PHP14相互作用的候选蛋白。

PHP14 was the only protein histidine phosphatase to be discovered in manmals. In our previous study, we found that the expression of PHP14 was associated with tumor invasion，but its biological function remains unclear. By RT-PCR and Western blot experiments, gene and protein expression was analysized between PHP14 knockdown and control cell lines. The result indicated that PHP14 modulated angiogenesis, tumorigenesis and metastasis by regulating expression of NF-κB and JNK downstream genes and proteins. Moreover, cells, knocking down PHP14, expressed less proteins related to cytoskeletal reorganization, which resulted in less filopodia formation and less bundles of actin filaments. These results are corresponding to previous finding that PHP14 knockdown cells showed decreasing potential of migration and invasion. Finally, several PHP14-interacting proteins were obtained by TAP purification and mass s8pectra analysis.