A Critical Role for Rac1 in Tumor Progression of Human Colorectal Adenocarcinoma Cells

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2008 Jan 1

PMID 18165265

Citations 25

Authors

Carolina Espina

Maria Virtudes Cespedes

Miguel Angel Garcia-Cabezas

Maria Teresa Gomez Del Pulgar

Alicia Boluda

Lourdes Garcia Oroz

Salvador A Benitah

Paloma Cejas

Manuel Nistal

Ramon Mangues

Juan Carlos Lacal

Affiliations

Soon will be listed here.

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.

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