A two-pronged attack: Why loss of STAT1 is bad news

February 29, 2012, University of Veterinary Medicine -- Vienna

Breast cancer represents about a fifth of all cancers diagnosed in women. The reasons for the rapid progression of the disease remain relatively poorly understood but recent work in the group of Veronika Sexl at the University of Veterinary Medicine, Vienna has pointed the finger strongly at loss or inactivation of the transcription factor STAT1. The results are published in the current issue of the journal Oncotarget.

The so-called signal transducers and activators of transcription (STATs) are involved in the regulation of cell division but details of their functions remain a matter of conjecture. In the development of breast cancer, the role of STAT1 is particularly interesting as high levels of STAT1 activity are known to be correlated with a better prognosis for breast cancer patients. There is a considerable body of evidence that STAT1 can act to suppress tumour growth in breast cancer but how does it function? Important clues are provided by the latest results of Christine Schneckenleithner and colleagues in the group of Veronika Sexl at the Vetmeduni Vienna.

By means of a series of sophisticated transplantation experiments in a mouse model, Schneckenleithner was able to show that in the absence of the STAT1 protein the mouse develops breast cancer more frequently, partly because the animal's immune system loses the ability to control developing tumours. Under normal circumstances, i.e. in the presence of STAT1, a type of known as cytotoxic or CTL recognizes and kills developing tumours as part of the body's normal tumour surveillance mechanism. In the absence of STAT1, however, the CTL can no longer perform this essential function, allowing cancer cells to grow unchecked (the other mechanism for killing tumour cells, involving "natural killer" cells, was found to play at best a very minor part in destroying , at least in this model system).

The loss of susceptibility to CTL enables to grow unimpeded. But Schneckenleithner's work also uncovered a further way in which STAT1 helps keep breast cancer in check. When the protein is removed from breast cells, there is an increased formation of small cancerous growths within the epithelia, known as mammary intraepithelial neoplasias or MINs. MINs arise as a result of accelerated cell division within the epithelial cells and are believed to represent a stepping-stone on the way to full-blown cancer. In other words, removing STAT1 is somehow interfering with a mechanism – presumably involving the transcription factor IRF1, which is known to be under the direct control of STAT1 – for preventing unwanted cell division.

The loss of STAT1 thus causes the development of via two mechanisms. Schneckenleithner summarizes the problem very neatly: "not only does deleting STAT1 cause the mice to develop more mini-cancers, it also prevents the main mechanism by which these are destroyed, leading to much faster tumour development." This double effect explains why the prognosis for with low activities of STAT1 is so poor and also points the way towards a possible treatment for this most widespread of cancers.

Explore further: Milk thistle extract stops lung cancer in mice

More information: The scientific article in full text online: www.impactjournals.com/oncotar … ath[]=371&path[]=625

Related Stories

Milk thistle extract stops lung cancer in mice

November 15, 2011
Tissue with wound-like conditions allows tumors to grow and spread. In mouse lung cancer cells, treatment with silibinin, a major component of milk thistle, removed the molecular billboards that signal these wound-like conditions ...

The good, the bad and the ugly: The many roles of c-JUN in cancer

June 28, 2011
The process of cell division is tightly regulated, as mistakes may lead to cancer. The so-called c-JUN protein has been fingered as causing tumors in both skin and liver. The group of Veronika Sexl at the University of Veterinary ...

Silencing a deadly conversation in breast cancer

June 2, 2011
While it is already known that breast cancer cells create the conditions for their own survival by communicating their needs to the healthy cells that surround them, Australian researchers have identified a new way of turning ...

Another step toward resisting breast cancer

September 21, 2011
Medical researchers at the University of Leeds have come a step closer to understanding how to stop breast cancers from coming back.

'If Hamlet give the first or second hit': The development of Burkitt's lymphoma

November 8, 2011
The human c-myc gene encodes a transcription factor (MYC) involved in the regulation of a vast number of other genes – it has been estimated that the transcription of about one in six genes is somehow under the control ...

Recommended for you

Study tracks evolutionary transition to destructive cancer

February 23, 2018
Evolution describes how all living forms cope with challenges in their environment, as they struggle to persevere against formidable odds. Mutation and selective pressure—cornerstones of Darwin's theory—are the means ...

Researchers use a molecular Trojan horse to deliver chemotherapeutic drug to cancer cells

February 23, 2018
A research team at the University of California, Riverside has discovered a way for chemotherapy drug paclitaxel to target migrating, or circulating, cancer cells, which are responsible for the development of tumor metastases.

Lab-grown 'mini tumours' could personalise cancer treatment

February 23, 2018
Testing cancer drugs on miniature replicas of a patient's tumour could help doctors tailor treatment, according to new research.

An under-the-radar immune cell shows potential in fight against cancer

February 23, 2018
One of the rarest of immune cells, unknown to scientists a decade ago, might prove to be a potent weapon in stopping cancer from spreading in the body, according to new research from the University of British Columbia.

Putting black skin cancer to sleep—for good

February 22, 2018
An international research team has succeeded in stopping the growth of malignant melanoma by reactivating a protective mechanism that prevents tumor cells from dividing. The team used chemical agents to block the enzymes ...

Cancer risk associated with key epigenetic changes occurring through normal aging process

February 22, 2018
Some scientists have hypothesized that tumor-promoting changes in cells during cancer development—particularly an epigenetic change involving DNA methylation—arise from rogue cells escaping a natural cell deterioration ...


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.