A critical role for Rac1 in tumor progression of human colorectal adenocarcinoma cells.
Colorectal adenocarcinoma is the second cause of cancer mortality in developed countries. Rac1 is a member of the family of Rho GTPases that regulates many intracellular signaling pathways, including those involved in tumorigenesis, invasion, and metastasis. We have investigated the role of Rac1 in colorectal tumor progression by genetic modification of the human colorectal adenocarcinoma cell line SW620 to either overexpress Rac1 or lack Rac1 expression. Tumor behavior was studied by orthotopic injection of stably modified cell lines into the cecal wall of athymic nude mice, a model that replicates the histopathological appearance and clinical behavior of human colorectal adenocarcinoma in humans. While overexpression of Rac1 resulted in an accelerated tumorigenic process, inducing a faster mortality rate, inhibition of Rac1 completely suppressed tumor formation. These results suggest that Rac1 plays a major role in colorectal adenocarcinoma progression. Finally, interference with Rac1 function may provide an important tool to block the malignant phenotype of colorectal adenocarcinoma cells.
Espina
Carolina
C
Translational Oncology Unit Consejo Superior de Investigaciones Cientificas-Universidad Autónoma de Madrid-La Paz, Centro Nacional de Biotecnología, Madrid, C/ Darwin 3, Campus de Cantoblanco, 28049 Madrid, Spain.
Céspedes
María Virtudes
MV
García-Cabezas
Miguel Angel
MA
Gómez del Pulgar
María Teresa
MT
Boluda
Alicia
A
Oroz
Lourdes García
LG
Benitah
Salvador A
SA
Cejas
Paloma
P
Nistal
Manuel
M
Mangues
Ramón
R
Lacal
Juan Carlos
JC
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009385:Neoplastic Processes; D015398:Signal Transduction; D013997:Time Factors; D020830:rac1 GTP-Binding Protein / Q000378:metabolism / Q000502:physiology*
C107953:RAC1 protein, human; D020830:rac1 GTP-Binding Protein