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Stem Cell Biology

The Brat that Causes Cancer

Groundbreaking research on tumor stem cells hints at a detailed understanding of cancerous growth – and perhaps at possibilities for therapy.

At a computer screen of the Vienna, Austria, based IMBA laboratories, one can observe in a live fruit fly Drosophila how a previously healthy cell all of a sudden turns into a malignant one and starts to grow into an ultimately deadly tumor cell. For the first time, researchers are also in a position to understand that a single missing protein called Brat is responsible for the crises.

“We could in fact identify Brat, a protein that normally inhibits uncontrolled growth in cells, to be the key in deciding whether a stem cell develops normally, or, if Brat is missing, it turns into a tumor”, says Juergen Knoblich who led the team of scientists whose findings will be published prominently in the next issue of the prestigious journal ‘Cell’.

With his research, Knoblich follows up on recent discoveries that reframed the most basic concepts of what tumors are. They are not just a bunch of cells gone wild altogether, but rather like any organ made of highly differentiated cells. Those who control the working and the growth of a tumor are like stem cells. Normally, when they divide, the result is one specialized cell for the organ, while the other retains the flexibility of stem cells and hence keeps the process of growth going in the healthy, controlled way.

Knoblich’s team now checked a large number of proteins which are involved in regulating growth. Among those, a singular and outstanding role is reserved for Brat: When a cell divides, Brat is transmitted in only one of the two resulting cells. Once the process of cell division is complete, Brat stops growth in this cell while in the other resulting cell, which lacks Brat, further divisions and growth will occur.

With Brat, Knoblich and his team identified the very first gene that controls growth in one of the two daughter cells of the division process. For the first time, they could exactly trace a gene that, if it is missing, turns a normal stem cell into a tumor cell. What makes the discovery in the tiny fly even more exciting is the fact that the same protein can be also found in human cells.

Of course, there are still open questions. First of all, additional tests will need to check if the same process works in human cells. However, a human homologue of Brat has been already suspected to be involved in tumor growth in humans. Another issue is to find out how exactly this protein operates within the metabolism of a cell, which are the genes that it interacts with, and how the entire regulatory system for growth ticks.

The new understanding of what makes a cell to become a tumor cell has enormous potential for research aiming at cancer therapies, Dr. Knoblich is confident. As only a few stem cells are ultimately responsible for tumor growth, any therapy must be specific enough to go just after those who are actually bad. With the identification of the protein in charge, a first hook has been found to look out for a future targeted cure.

“It is like chasing a swarm of bees, or ants”, Dr. Knoblich explains. “It is worthless to catch any number of individuals as long as you don’t get hold of the queen.”

Jürgen Knoblich
Jürgen Knoblich was born in Memmingen (Germany) in 1963. He studied Biochemistry in Tübingen and London and gradually focussed his research interest on the development of the fruit fly Drosophila.

Following his PhD in 1994, Jürgen Knoblich went to San Francisco to carry out postdoctoral research at the laboratory of Yuh Nung Jan at UCSF. In 1997, Dr. Knoblich moved to Vienna, Austria, where he took up a position as Group Leader at the Research Institute of Molecular Pathology (IMP). Since 2004, he has been Senior Scientist and Deputy Director at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA).

Jürgen Knoblich’s contributions to developmental biology have been acknowledged by Awards from the European associations EMBO, FEBS and ELSO.

IMBA, the Institute of Molecular Biotechnology of the Austrian Academy of Sciences, combines basic and applied research in the area of biomedicine. Interdisciplinary research groups work towards understanding the fundamental molecular underpinnings of normal and pathological behavior. The ultimate aim is to translate this knowledge into novel approaches for diagnosis, prevention and therapy of diseases. IMBA is financed by the City of Vienna and the Austrian Government.

IMP- IMBA Research Center
The Research Institute of Molecular Pathology (IMP), established in 1988 by Boehringer Ingelheim, and the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), which went into operation in 2003, have agreed on a close research collaboration. Under the name “IMP-IMBA Research Center”, the two institutes share most of the administrative and scientific infrastructure. Together, IMBA and IMP employ over 300 people from 30 different nations. Both institutes are members of the “Campus Vienna Biocenter”.