Loss of Rb Cooperates with Ras to Drive Oncogenic Growth in Mammalian Cells

Melissa J. Collins, Ilaria Napoli, Sara Ribeiro, Sinead Roberts and Alison C. Lloyd 2012. Loss of Rb Cooperates with Ras to Drive Oncogenic Growth in Mammalian Cells. Current Biology. 22 (19), pp. 1765-1773. https://doi.org/10.1016/j.cub.2012.07.040

TitleLoss of Rb Cooperates with Ras to Drive Oncogenic Growth in Mammalian Cells
TypeJournal article
AuthorsMelissa J. Collins, Ilaria Napoli, Sara Ribeiro, Sinead Roberts and Alison C. Lloyd
Abstract

Background

The p53, Rb, and Ras/PI3K pathways are implicated in the development of the majority of human cancers. A number of studies have established that these pathways cooperate at the level of the cell cycle leading to loss of normal proliferative controls. Here we have investigated how these signals influence a second critical component of tumor formation—cell growth.

Results

We find that oncogenic Ras is sufficient to drive growth via the canonical growth pathway, PI3K-AKT-TOR; however, it does so relatively weakly and p53 loss does not drive cell growth at all. Importantly, we identify a novel role for the Rb family of tumor suppressors in directing cell growth via a signaling pathway distinct from PI3K-AKT-TOR and via an E2F-independent mechanism. However, we find that strong, sustained growth requires Rb loss together with Ras signaling, identifying an additional mechanism by which these oncogenic pathways cooperate and a critical role for Ras in preserving the uptake of extracellular nutrients required for biogenesis.

Conclusions

We have identified a new role for the Rb family in cell biogenesis and show that, as for other processes associated with tumor development, oncogenic cell growth is dependent on cooperating oncogenes.

JournalCurrent Biology
Journal citation22 (19), pp. 1765-1773
ISSN0960-9822
Year2012
PublisherCell Press
Publisher's version
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.1016/j.cub.2012.07.040
Publication dates
Published09 Oct 2012

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