Tchevkina Elena, Agapova Larisa, Dyakova Natalya, Martinjuk Anna, Komelkov Andrei, Tatosyan Alexander
Institute of Carcinogenesis, Cancer Research Center, 115478 Moscow, Russia.
Oncogene. 2005 Jan 13;24(3):329-35. doi: 10.1038/sj.onc.1208094.
RAS oncogenes play a critical role in oncogenic transformation and metastases formation. Here we show that Ha-ras greatly stimulates spontaneous metastatic activity of transformed cells through the Ras/RalGDS/RalA intracellular signaling pathway. Introduction of RalA alone leads to a drastic increase of metastatic activity of transformed cells. We demonstrate that metastatic ability of cells could be dramatically enhanced by RalA stimulation or, conversely, hampered by RalA suppression. Furthermore, we found that during in vivo selection cells acquire high metastatic properties as a result of endogenous RalA activation. The ability of RalA to induce metastasis was demonstrated in spontaneously transformed as well as in virus transformed fibroblasts.
RAS致癌基因在致癌转化和转移形成过程中发挥着关键作用。在此我们表明，Ha-ras通过Ras/RalGDS/RalA细胞内信号通路极大地刺激了转化细胞的自发转移活性。单独引入RalA会导致转化细胞的转移活性急剧增加。我们证明，RalA刺激可显著增强细胞的转移能力，反之，RalA抑制则会阻碍细胞的转移能力。此外，我们发现，在体内选择过程中，细胞由于内源性RalA激活而获得高转移特性。RalA诱导转移的能力在自发转化以及病毒转化的成纤维细胞中均得到了证实。
