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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 4/2007

01-04-2007 | Original Article

R-Ras promotes metastasis of cervical cancer epithelial cells

Authors: Nancy Mora, Ricardo Rosales, Carlos Rosales

Published in: Cancer Immunology, Immunotherapy | Issue 4/2007

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Abstract

Mutations in the small GTPase R-Ras that promote constitutive activation of this signaling molecule have been observed in a variety of invasive cancer cell types. We previously reported that expression of an oncogenic form of R-Ras (R-Ras87L) in a cell line of cervical cancer (C33A cells) augments cell growth in vitro and tumorigenicity in vivo. Because increased tumorigenicity in vivo often precedes metastasis, we now examined whether the expression of R-Ras87L also increased the metastatic potential of C33A cells. Accelerated tumor growth was observed in athymic mice after subcutaneous injection of R-Ras87L-expressing C33A cells. In addition, increased metastasis to the liver, in immunodeficient SCID mice, was observed after intravenous injection of R-Ras87L-expressing C33A cells. Also, R-Ras87L-expressing cells presented decreased membrane expression of MHC class I molecules, and β1 integrins, but increased levels of PI 3-K and Akt activities. C33A cells expressing R-Ras87L also migrated more over collagen I in wound assays. Inhibition of the PI 3-K/Akt/mTOR pathway by pharmacological means blocked R-Ras87L-induced accelerated growth and migration over collagen I. These results suggest oncogenic R-Ras has a central role in cancer progression towards a metastatic phenotype, through the activation of the PI 3-K/Akt/mTOR signaling pathway.
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Metadata
Title
R-Ras promotes metastasis of cervical cancer epithelial cells
Authors
Nancy Mora
Ricardo Rosales
Carlos Rosales
Publication date
01-04-2007
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 4/2007
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-006-0205-z

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