- Obesity is associated with aggressive forms of breast cancer.
- Obesity releases cytokines into the bloodstream and impacts the metabolism of breast cancer cells making them more aggressive.
- Metastasis of breast cancer or recurrence after surgery is the main cause of cancer-related deaths in women.
Fatty acid precursors promote metastases
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 Marcos Rios Garcia, 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. "Blocking the signaling pathways and switching off the metastasis-related genes could be a therapeutic target," Herzig said. "As part of the so-called neoadjuvant therapy, the risk of metastases or the recurrence of tumors could be reduced prior to the surgical removal of the tumor."
References:
- Marcos Rios Garcia et al,. Acetyl-CoA Carboxylase 1-Dependent Protein Acetylation Controls Breast Cancer Metastasis and Recurrence, Cell Metabolismhttps://doi.org/10.1016/j.cmet.2017.09.018