Important factor in metastasis of breast cancer mapped

Stopping cancer cells from spreading could be one way of preventing the progression of cancer. Now researchers at Karolinska Institutet and the Universities in Umeå and Lund have discovered a key molecule with an important role in the spread of breast cancer cells – a factor that could prove the basis for future drugs. The study has been published in the scientific journal Oncogene.

The primary reason that people die from cancer is because the cancer cells spread to vital organs such as the lungs and liver. But in spite of intensive research we still know only little about how cancer cells spread and what factors regulate this. Consequently, there are few drugs available that can act on the metastatic process. But now a group of researchers at Karolinska Institutet and Umeå University have discovered a molecule that plays a key role in the spread of breast cancer.

"The transcription factor C/EBPbeta acts by regulating the cancer cells' ability to spread and form metastases through its function as a type of relay in breast cancer cells. When it is active it helps to maintain benign growth but, if it becomes inactive, these functions are lost and cancer cells start to spread", relates Jonas Fuxe, lecturer at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet and the study project manager.

In adults, cancers originate most frequently in the so-called epithelial cells, i.e. the cells that form the barrier against the surroundings, for example in the skin, airways and mammary glands. Crucial to their function is the ability to bind to each other. Recently it has been shown that certain inflammatory signals that often occur in tumours, such as TGF-beta (transforming growth factor beta), can make cancer cells spread by activating a process called EMT, "epithelial-mesenchymal transition". Cancer cells that undergo EMT lose their ability to adhere to each other and can therefore migrate away from the original tumour.

"We have investigated whether C/EBPbeta is connected to EMT in breast cancer. We found that C/EBPbeta was inactivated in invasive breast cancer through a microRNA and that this resulted in breast cancer cells loosing their resistance to undergo EMT. The cells become susceptible and undergo EMT, and can then spread", comments Fuxe.

Thus, when the C/EBPbeta factor is active in the cells, it helps to maintain functioning epithelial cells thereby counteracting EMT, but when it becomes inactive these functions are lost.

"This means that a drug that strengthens the function of C/EBPbeta might be able to prevent the spread of the breast cancer", states Jonas Fuxe in conclusion.

The research has been financed by the Swedish Cancer Society, the Swedish Childhood Cancer Foundation, the Swedish Research Council, the Swedish Society for Medical Research (SSMF), and the Karolinska Institute Strategic Research Programme in Cancer, StratCan.

Publication

MiR-155-mediated loss of C/EBPβ shifts the TGF-β response from growth inhibition to epithelial-mesenchymal transition, invasion and metastasis in breast cancer
J Johansson, T Berg, E Kurzejamska, M-F Pang, V Tabor, M Jansson, P Roswall, K Pietras, M Sund, P Religa, and J Fuxe
Oncogene (2013) 32, 5614–5624; doi:10.1038/onc.2013.322; published online 19 August 2013