Researchers discover a tumor suppressor gene in a very aggressive lung cancer

2014-01-09

(Press-News.org) Contact information: Arantxa Mena
amena@idibell.cat
34-932-607-282
IDIBELL-Bellvitge Biomedical Research Institute
Researchers discover a tumor suppressor gene in a very aggressive lung cancer

In addition to identifying the tumor suppressor role of MAX in lung cancer, the group led by Montse Sanchez-Cespedes has unveiled a functional relationship between MAX and another tumor suppressor, BRG1, in virtue of which BRG1 regulates the expression of MAX through direct recruitment to the MAX promoter. However, the functional connection is even more complex. On one hand, the presence of BRG1 is required to activate neuroendocrine transcriptional programs and to up-regulate MYC-targets, such as glycolytic-related genes. Moreover, the depletion of BRG1 strongly hinders cell growth, specifically in MAX-deficient cells, heralding a synthetic lethal interaction. The preferential toxicity of the inactivation of BRG1 in MAX-deficient lung cancer cells opens novel therapeutic possibilities for the treatment of SCLC patients with MAX-deficient tumors.

The Genes and Cancer group has identified several genes altered in lung cancer. Among these is BRG1 (also called SMARCA4) and the latest generation-sequencing technologies have extended these findings to other tumor types evidencing that BRG1 inactivation is widespread in cancer. BRG1 encodes one ATPase of the SWI/SNF chromatin remodeling complex and Dr. Sanchez-Cespedes group had previously shown that loss of BRG1 is closely related to the activation of MYC in lung cancer. Both conditions are mutually exclusive and act preventing cell differentiation and promoting cell growth. The current discovery that MAX acts as a tumor suppressor in lung cancer provides evidence that an aberrant SWI/SNF-MYC/MAX network is essential for lung cancer development.

INFORMATION:

Reference:

Romero OA, Torres-Diz M, Pros E, Savola S, Gomez A, Moran S, Saez C, Iwakawa R, Villanueva A, Montuenga LM, Kohno T, Yokota J, Sanchez-Cespedes M.MAX inactivation in small-cell lung cancer disrupts the MYC-SWI/SNF programs and is synthetic lethal with BRG1. Cancer Discovery. 2013 Dec 20. [Epub ahead of print].

Related references:

Romero OA, Sanchez-Cespedes M.The SWI/SNF genetic blockade: effects in cell differentiation, cancer and developmental diseases. Oncogene. 2013 Jun 10. [Epub ahead of print]

Romero OA, Setien F, John S, Gimenez-Xavier P, Gómez-López G, Pisano D, Condom E, Villanueva A, Hager GL, Sanchez-Cespedes M.The tumour suppressor and chromatin-remodelling factor BRG1 antagonizes Myc activity and promotes cell differentiation in human cancer. EMBO Mol Med. 2012 Jul;4(7):603-16.

Referencia del artículo:

Romero OA, Torres-Diz M, Pros E, Savola S, Gomez A, Moran S, Saez C, Iwakawa R, Villanueva A, Montuenga LM, Kohno T, Yokota J, Sanchez-Cespedes M.MAX inactivation in small-cell lung cancer disrupts the MYC-SWI/SNF programs and is synthetic lethal with BRG1. Cancer Discovery. 2013 Dec 20. [Epub ahead of print].

Articulos relacionados:

Romero OA, Sanchez-Cespedes M.The SWI/SNF genetic blockade: effects in cell differentiation, cancer and developmental diseases. Oncogene. 2013 Jun 10. [Epub ahead of print]

Romero OA, Setien F, John S, Gimenez-Xavier P, Gómez-López G, Pisano D, Condom E, Villanueva A, Hager GL, Sanchez-Cespedes M.The tumour suppressor and chromatin-remodelling factor BRG1 antagonizes Myc activity and promotes cell differentiation in human cancer. EMBO Mol Med. 2012 Jul;4(7):603-16.

ELSE PRESS RELEASES FROM THIS DATE:

Maternal stress hormones and maternal smoking increase daughter's risk of nicotine dependence

2014-01-09

Maternal stress hormones and maternal smoking increase daughter's risk of nicotine dependence Reports new study in Biological Psychiatry Philadelphia, PA, January 9, 2014 – Tobacco smoking by pregnant women has long been viewed as a public health risk because of smoking's ...

Kids have skewed view of gender segregation

2014-01-09

Kids have skewed view of gender segregation Children believe the world is far more segregated by gender than it actually is, implies a new study led by a Michigan State University scholar. Jennifer Watling Neal and colleagues examined classroom friendships in five ...

Many men start testosterone therapy without clear medical need

2014-01-09

Many men start testosterone therapy without clear medical need Study finds increased testing among men with normal hormone levels Chevy Chase, MD—Although testosterone use has sharply increased among older men in the past decade, many patients appear to have ...

Lions are critically endangered in West Africa

2014-01-09

Lions are critically endangered in West Africa New York, NY – A report published today concludes that the African lion is facing extinction across the entire West African region. The West African lion once ranged continuously from Senegal to Nigeria, but the new paper reveals ...

Acid mine drainage reduces radioactivity in fracking waste

2014-01-09

Acid mine drainage reduces radioactivity in fracking waste 2 wrongs could make a right in mining wastewater DURHAM, NC -- Much of the naturally occurring radioactivity in fracking wastewater might be removed by blending it with another wastewater from acid mine drainage, according ...

When charitable acts are 'tainted' by personal gain

2014-01-09

When charitable acts are 'tainted' by personal gain We tend to perceive a person's charitable efforts as less moral if the do-gooder reaps a reward from the effort, according to new research. This phenomenon — which researchers call ...

A powerful technique to further understanding of RNA

2014-01-09

A powerful technique to further understanding of RNA Qi Zhang sees himself as a warrior. In his lab at the University of North Carolina at Chapel Hill, he wages war on genetic diseases such as cancer and heart disease on a battlefield measured ...

Extraordinary sensors pushed to their boundaries

2014-01-09

Extraordinary sensors pushed to their boundaries A new step is being taken in the development of ultra-stable sensors of small forces Last year, Tobias Kippenberg and his team from the Laboratory of Photonics and Quantum Measurements ...

Funding problems threaten US disaster preparedness

2014-01-09

Funding problems threaten US disaster preparedness A study by researchers at the George Washington University, the University of Southern California, and the Cabarrus Health Alliance lists seven recommendations to enhance preparedness for public health emergencies ...

Iconic Australasian trees found as fossils in South America

2014-01-09

Iconic Australasian trees found as fossils in South America Today in Australia they call it Kauri, in Asia they call it Dammar, and in South America it does not exist at all unless planted there; but 52 million years ago the giant coniferous evergreen tree known to botanists ...