title: A critical role for Rac1 in tumor progression of human colorectal adenocarcinoma cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Carolina
authors.initials: C
authors.lastname: Espina
authors.forename: María Virtudes
authors.initials: MV
authors.lastname: Céspedes
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: García-Cabezas
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Gómez del Pulgar
authors.forename: Alicia
authors.initials: A
authors.lastname: Boluda
authors.forename: Lourdes García
authors.initials: LG
authors.lastname: Oroz
authors.forename: Salvador A
authors.initials: SA
authors.lastname: Benitah
authors.forename: Paloma
authors.initials: P
authors.lastname: Cejas
authors.forename: Manuel
authors.initials: M
authors.lastname: Nistal
authors.forename: Ramón
authors.initials: R
authors.lastname: Mangues
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Lacal
mesh_terms: 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*
chemical_list: C107953:RAC1 protein, human; D020830:rac1 GTP-Binding Protein