Metastasis is the leading cause of mortality in patients with highly invasive cancers and, as such, is a major problem for medicine. It has been increasingly recognized that cancer-related inflammation plays an important role in promoting invasion and the metastatic process in which cell motility and upregulation of proteolytic enzymes are crucial events. TNFα is a proinflammatory cytokine known to stimulate synthesis of MMP9, a zinc- and calcium-dependent endopeptidase contributing to the regulation of ECM remodeling and cell signaling. However, the precise molecular mechanism of TNFα-induced MMP9 gene expression in cancers is still not fully understood. This study shows that TNFα-induced cell migration and invasion involve ERK1/2-dependent up-regulation of CDKN1A/p21 expression in highly aggressive breast cancer cells and that CDKN1A/p21 plays an important regulatory role in TNFα-induced MMP9 gene expression, indicating an unknown function of CDKN1A/p21 as a regulator of proteolytic activity in cancer cells.

转移是高度浸润性癌症患者死亡的主要原因，因此，转移是医学上的主要问题。人们日益认识到，与癌症有关的炎症在促进侵袭和转移过程中起着重要作用，在转移过程中，细胞运动性和蛋白水解酶的上调是关键事件。TNFα是一种促炎细胞因子，已知能刺激MMP9的合成，MMP9是锌和钙依赖性内肽酶，有助于调节ECM重塑和细胞信号传导。但是，肿瘤中TNFα诱导的MMP9基因表达的确切分子机制仍不完全清楚。