TY - JOUR
T1 - Activation of RalA is critical for Ras-induced tumorigenesis of human cells
AU - Lim, Kian Huat
AU - Baines, Antonio T.
AU - Fiordalisi, James J.
AU - Shipitsin, Michail
AU - Feig, Larry A.
AU - Cox, Adrienne D.
AU - Der, Channing J.
AU - Counter, Christopher M.
N1 - Funding Information:
We thank X.F. Wang, A.D. Proia, and D. Tyler for reagents and S.J. Adams, T. Veldman, and D. Lew for review of the manuscript. This work was supported by NCI grants CA94184 (C.M.C.) and CA42978 (A.D.C. and C.J.D.) and by the Lustgarten Foundation for Pancreatic Cancer Research grant LF-056 (A.D.C.). K.-H.L. is a Department of Defense Breast Cancer Research Predoctoral Scholar. C.M.C. is a Leukemia and Lymphoma Scholar.
PY - 2005/6
Y1 - 2005/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=20444410041&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2005.04.030
DO - 10.1016/j.ccr.2005.04.030
M3 - Article
C2 - 15950903
AN - SCOPUS:20444410041
SN - 1535-6108
VL - 7
SP - 533
EP - 545
JO - Cancer Cell
JF - Cancer Cell
IS - 6
ER -