The small G-protein RalA stimulates metastasis of transformed cells.
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.
Institute of Carcinogenesis, Cancer Research Center, 115478 Moscow, Russia.
Elena
E
Tchevkina
Larisa
L
Agapova
Natalya
N
Dyakova
Anna
A
Martinjuk
Andrei
A
Komelkov
Alexander
A
Tatosyan
D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D017931:DNA Primers; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000502:physiology; D008647:Mesocricetus; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000473:pathology*; D020725:ral GTP-Binding Proteins / Q000502:physiology*
D017931:DNA Primers; D020725:ral GTP-Binding Proteins