New Pathway to Control Breast Cancer Metastasis and Recurrence

The number of people with obesity is increasing rapidly worldwide. The German Cancer Research Center (DKFZ) recently reported that according to the WHO the number of children and adolescents with obesity increased tenfold between 1975 and 2016. Severe overweight can lead to various health impairments. Besides inducing cardiovascular diseases, obesity for example also promotes the development of cancer and metastases.

Obesity leads to the release of cytokines into the bloodstream which impact the metabolism of breast cancer cells, making them more aggressive as a result, according to a report published in 'Cell Metabolism'. The team has already been able to halt this mechanism with an antibody treatment.

The current study elucidates an as yet unknown mechanism making breast cancer more aggressive. The enzyme ACC1(acetyl-CoA carboxylase) plays a central role in this process," said the study lead. "ACC1 is a key component of fatty acid synthesis," said the author. "However, its function is impaired by the cytokines leptin and TGF-β." The levels of these cytokines are increased particularly in the blood of severely overweight subjects.

The scientists demonstrated that the described inhibition of ACC1 leads to the accumulation of the fatty acid precursor acetyl-CoA. This precursor is transferred to certain gene "switches" that in turn increase the metastatic capacity of cancer cells by activating a specific gene program.

"Using human tissue from breast cancer metastases, we were able to show that ACC1 was significantly less active there," said first author of the study. When the scientists blocked the as yet unknown signaling pathway with an antibody (directed against the leptin receptor), this led to a significantly reduced metastatic spread of breast cancer tumors in an experimental model.

In the future, the researchers want to substantiate the data on the newly discovered mechanism in further studies. In addition, they are also considering related intervention points that could possibly be exploited therapeutically.

https://www.helmholtz-muenchen.de/en/news/latest-news/press-information-news/article/42901/index.html