Welcome to Pujana's Laboratory

How cancer cells adapt to mTOR inhibition?

Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition

Oncogene (2016), 1–13.

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

Science matters

Spanish political leaders lack honesty and professionalism in many aspects of their work, including their approach to science and research. It is not true that they envision a change in the production model; they do not take decisions that would lead to such a change and simply wait for the "services" model to regain its strength. Decisions are often arbitrary and motivated principally by personal agendas. The statements made in the last years saying that research and science should be the driving force of the new economy, and that they will not cut research funding, were lies.

Nature

Science

Save Science

Leaving Spain

D-Recerca

 

2014
"Presupuestos Generales del Estado 2014: Nuevo hachazo a la ciencia española"

2013
L Guindos, Minister of Economy, Spain: "la I+D+i será "prioritaria" en los presupuestos de 2014"

2005
"La investigación será prioritaria en los próximos presupuestos"

1997
"Aznar subraya que la investigación es uno de los fundamentos prioritarios de su política"

 

Some R & D expenditure facts:

2012 Spain 1.30% of GDP; while Euro area average was 2.14% 

2012 Catalonia was 1.51% same year.

 

Catalonia, a different country, but needs improvement

From 2001, Catalonia has developed a strong and top-quality biomedical research network. The model is based on leading institutes and investigators, which are outperformers in many aspects including fund raising and peer-review publications. The ICREA program has been key to achieve this situation, but in my opinion there is much to improve. In a scenario where the Catalan government has not its own competitive research grants, accountability for the ratio of goverment support received versus scientific impact is urgently need. Most importantly, we should be able to explain how we expend money and which is the impact in improving global health care and economic productivity. We should not anymore accept press-release statements like "our results will improve cancer cure in 5 years", "our results will open new precise/efficient therapies" if after that that period there is not expert review of the consequences of the research findings and fund expenses.

Education for our kids

If science has a minor role in primary education, we cannot aim (some don't want to) at our society becoming more critical, fair and prosperous. I agree that today's general lack of creativity and critical thinking is partially due to the rigidity of the educational curriculum, where science and tech has a minor role. Teaching by observing, discussing and reasoning the surrounding world has the potential to build a better and fairest society. The corresponding skills would also be fundamental in every part of a person live. Fortunately, we are changing our schools but it seems that it will take much long that the change wave arrives to our universities; this is an urgent need if we also want to consolidate the Catalan research network, including talented and well trained PhD students that will be future leaders.

Mission

Open positions (pre and postdoctoral; mail to: procureico at gmail.com)

The Catalan Institute of Oncology (ICO) is a public center working exclusively in the field of cancer. Its approach to the disease is comprehensive, combining, all in one organization, prevention, care, specialized training and research. The ICO was founded in 1996 and has become a center of reference in Catalonia, both in healthcare quality and in research (top Spanish hospital-institute in terms of scientific impact). The Pujana's research group is part of the newly created ICO ProCURE research program, aimed at addressing a major clinical problem in oncology; the existence or emergence of cancer therapeutic resistance. The group is located in the Bellvitge Institute for Biomedical Research (IDIBELL) campus.

grup 2016 2

Selected publications

2016. Cancer network activity associated with therapeutic response and synergism. Genome Medicine 24;8(1):88.

2015. Integrating germline and somatic data towards a personalized cancer medicine. Trends Molecular Medicine 20(8):413-5.

2011. Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer. PLoS Biology Nov;9(11):e1001199.

2010. Biological reprogramming in acquired resistance to endocrine treatment of breast cancer. Oncogene 29(45):6071-83.

2007. Network modeling links breast cancer susceptibility and centrosome dysfunction. Nature Genetics 39(11):1338-49.