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Obesity and breast cancer

Researchers reveal how obesity promotes breast cancer

3D spheroid of cultivated breast cancer cells. Invasive cells show a light blue co-staining for the leptin receptor and a marker of epithelial-mesenchymal. Cell nuclei are stained in red. (Credit: Helmholtz Zentrum München)
When the scientists blocked the as yet unknown signalling pathway with an antibody - directed against the leptin receptor - this led to a significantly reduced metastatic spread of breast cancer tumours in an experimental model

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 research by scientists from Helmholtz Zentrum München, Technische Universität München (TUM) and Heidelberg University Hospital, Germany.

“The enzyme ACC1 plays a central role in this process," said Dr Mauricio Berriel Diaz, deputy director of the Institute for Diabetes and Cancer (IDC) at Helmholtz Zentrum München, who led the study together with Stephan Herzig, director of the IDC and professor for Molecular Metabolic Control at TUM and Heidelberg University Hospital. "ACC1 is a key component of fatty acid synthesis. However, its function is impaired by the cytokines leptin and TGF-β."

The study, ‘Acetyl-CoA Carboxylase 1-Dependent Protein Acetylation Controls Breast Cancer Metastasis and Recurrence, Cell Metabolism,’ published in the journal, Cell Metabolism, explains an as yet unknown mechanism making breast cancer more aggressive. The found that the levels of these cytokines are increased particularly in the blood of severely overweight subjects.

The scientists have 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 Marcos Rios Garcia, first author of the study.

When the scientists blocked the as yet unknown signalling pathway with an antibody (directed against the leptin receptor), this led to a significantly reduced metastatic spread of breast cancer tumours 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.

"Blocking the signalling pathways and switching off the metastasis-related genes could be a therapeutic target," said Herzig. "As part of the so-called neoadjuvant therapy, the risk of metastases or the recurrence of tumours could be reduced prior to the surgical removal of the tumour." 

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