Self-regulating networks dictate the genetic program of tumor cells

September 25, 2012, Charité - Universitätsmedizin Berlin

Scientists at Charité – Universitätsmedizin Berlin could explain a yet unknown regulatory network that controls the growth of tumor cells. Understanding such networks is an important task in molecular tumor biology in order to decode the relationships between the determinants defining which molecules are produced and in what quantities, in both normal and tumor cells. The study is published in the journal Molecular Systems Biology.

The growth of a tumor and its reaction to specifically targeted therapy is dictated by changes in its genetic material (mutations) encoding special signal molecules. These molecules activate the genetic program of tumor cells via branched signalingpathways and influence all processes needed for cell division, the mobility of cells and metastasis. Significant steering elements of these tumor-specific programs are called transcription factors. These are molecules that selectively control the transcription of the cell's genetic information (DNA) into and enable production of proteins . Altogether a complex network of mutually regulating transcription factors is activated.

Whereas the signal network in human tumors has already been characterized very well, it is hardly understood how transcription factors cooperate and regulate each other. In order to explain this transcription factor network, the scientists used a approach. A complex experimental data set—in which the in were systematically disrupted—was analyzed with the help of mathematical modeling. As a result, interactions within the network could be reconstructed and the network controlling tumor growth clarified.

"Contrary to a current assumption, the results show that no superordinate transcription factor exists that controls the activity of other factors as a master regulator," explains Prof. Reinhold Schäfer, head of the Laboratory for Molecular Tumor Pathology and deputy director of the Charité Comprehensive Cancer Center. Instead, two hierarchical groups of interacting factors exist. Each of them activates gene sets needed for growth and cancer-specific properties of the cells. The results indicate that new therapeutic approaches against tumors must target multiple rather than singular factors and consider the network structures.

Explore further: What causes brain cancer? Understanding glioblastoma at the genetic, molecular level

More information: Stelniec-Klotz I, Legewie S, Tchernitsa O, Witzel F, Klinger B, Sers C, Herzel H, Blüthgen N, Schäfer R. Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS. Mol Syst Biol. 2012 Jul 31;8:601. doi: 10.1038/msb.2012.32

Related Stories

What causes brain cancer? Understanding glioblastoma at the genetic, molecular level

July 6, 2011
Glioblastoma is the most common and most lethal form of brain tumor in people. Research published in the International Journal of Computational Biology and Drug Design offers a novel way to determine what biological functions ...

Researchers and colleagues identify PHF20, a regulator of gene P53

August 24, 2012
Researchers at Moffitt Cancer Center and colleagues have identified PHF20, a novel transcriptional factor, and clarified its role in maintaining the stability and transcription of p53, a gene that allows for both normal cell ...

Disappearance of genetic material allows tumor cells to grow

August 4, 2011
Malignant Sézary syndrome is characterized by the reproduction of a special type of white blood cells in the skin of male and female patients. In contrast to most other skin lymphomas, patients with Sézary syndrome ...

Recommended for you

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018
WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers ...

Researchers identify new treatment target for melanoma

January 16, 2018
Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous ...

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

Dietary fat, changes in fat metabolism may promote prostate cancer metastasis

January 15, 2018
Prostate tumors tend to be what scientists call "indolent" - so slow-growing and self-contained that many affected men die with prostate cancer, not of it. But for the percentage of men whose prostate tumors metastasize, ...

Pancreatic tumors may require a one-two-three punch

January 15, 2018
One of the many difficult things about pancreatic cancer is that tumors are resistant to most treatments because of their unique density and cell composition. However, in a new Wilmot Cancer Institute study, scientists discovered ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.