Activation of RalA is critical for Ras-induced tumorigenesis of human cells

Kian Huat Lim, Antonio T. Baines, James J. Fiordalisi, Michail Shipitsin, Larry A. Feig, Adrienne D. Cox, Channing J. Der, Christopher M. Counter

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Abstract

RalGEFs were recently shown to be critical for Ras-mediated transformed and tumorigenic growth of human cells. We now show that the oncogenic activity of these proteins is propagated by activation of one RalGEF substrate, RalA, but blunted by another closely related substrate, RalB, and that the oncogenic signaling requires binding of the RalBP1 and exocyst subunit effector proteins. Knockdown of RalA expression impeded, if not abolished, the ability of human cancer cells to form tumors. RalA was also commonly activated in a panel of cell lines from pancreatic cancers, a disease characterized by activation of Ras. Activation of RalA signaling thus appears to be a critical step in Ras-induced transformation and tumorigenesis of human cells.

Original languageEnglish
Pages (from-to)533-545
Number of pages13
JournalCancer Cell
Volume7
Issue number6
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

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    Lim, K. H., Baines, A. T., Fiordalisi, J. J., Shipitsin, M., Feig, L. A., Cox, A. D., Der, C. J., & Counter, C. M. (2005). Activation of RalA is critical for Ras-induced tumorigenesis of human cells. Cancer Cell, 7(6), 533-545. https://doi.org/10.1016/j.ccr.2005.04.030