the web site of the Cell Proliferation Group. The Group is led
by Jesús Gil and was
established in November 2005. We are part of the Epigenetics,
Development and Cancer Section at the Medical
Research Council (MRC) Clinical Sciences Centre (CSC). The
CSC is core-funded by the MRC,
a division of the Faculty
of Medicine of Imperial
College London, and is located on the Hammersmith
Hospital Campus. Our group is a young and friendly team
that hopefully will be expanding in the coming years. We use
mammalian cell culture systems and genetic
screenings to identify genes potentially involved in cancer
progression. Here you will find more information about our group
and the research we do. We encourage you to contact
us if you have any questions about the Group or this site,
or if you would like to join us.
The ultimate goal of the Cell
Proliferation Group is to identify novel genes
involved in cancer and analyse how they are related to the genetic
networks regulating cell proliferation. Normal cells have a
limited ability to proliferate. When primary cells reach this
limit or upon the expression of some oncogenes, they undergo
an irreversible growth arrest, termed senescence.
Our Group works on understanding senescence because it suppresses
tumor progression (Collado et al. 2005) and since we can also use it as a model
system to identify novel cancer genes (Gil et al. 2004; Kondo et al. 2005). Using genetic
screenings, we have identified the unexpected role of glycolytic
enzymes in senescence and cancer (Kondoh et al. 2005) and how chemokine signaling
reinforces senescence (Acosta et al. 2008). In addition, we have identified the
Polycomb group (PcG) CBX7 as a gene modulating cellular lifespan
(Gil et al. 2004) by repressing the transcription of the INK4A/ARF locus (Gil and Peters, 2006)
and therefore interfering with the Rb and p53 pathways. Cbx7
has oncogenic properties and its expression is upregulated in
Genetic screens to identify
cancer genes. This is an outline of the
experimental approach used by our group. Retroviral libraries
are transfected into packaging cell lines, and high-titre
viral supernatants are used to infect the target cells
in which functional screenings will be carried out. Vectors
conferring a given phenotype (such as bypassing of senescence)
are recovered, retested and identified.
Acosta, J. C., O'Loghlen, A., Banito, A., Guijarro, M. V., Augert,
A., Raguz, S., Fumagalli, M., Da Costa, M., Brown, C., Popov,
N., Takatsu, Y., Melamed, J., d'Adda di Fagagna, F., Bernard,
D., Hernando, E. and Gil, J. (2008). Chemokine
signaling via the CXCR2 receptor reinforces senescence.
Cell 133, 1006–1018.
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Collado, M., Gil, J., Efeyan, A., Guerra, C., Schumacher, A.
J., Barradas, M., Benguría, A, Zaballos, A., Flores,
J. M., Barbacid, M., Beach, D. and Serrano M. (2005). Tumor
biology: senescence in premalignant tumours. Nature 436, 642.
Gil, J., Bernard, D., Martinez, D. and Beach, D. (2004). Polycomb
CBX7 has a unifying role in cellular lifespan. Nature
Cell Biology 6, 67-72.
Gil, J. and Peters, G. (2006). Regulation
of the INK4b-ARF-INK4a tumour suppressor locus:
all for one or one for all. Nature Reviews Molecular
Cell Biology 7, 667-677.
Kondoh, H., Lleonart, M. E., Gil, J., Wang, J., Degan, P., Peters,
G., Martinez, D., Carnero, A. and Beach, D. (2005). Glycolytic
enzymes can modulate cellular lifespan. Cancer Research 65, 177-185.
Scott, C. L., Gil, J., Hernando, E., Teruya-Feldstein, J., Narita,
M., Martinez, D., Visakorpi, T., Mu, D., Cordon-Cardo, C., Peters,
G., Beach, D. and Lowe, S. W. (2007). Role
of the chromobox protein CBX7 in lymphomagenesis. Proceedings
of the National Academy of Science of the United States of America 104, 5389-5394.
] [ FULL