Breast cancer study reveals new pathways for metastasis

Live 2017

Dr. Peter Siegel

By Stephanie Malley, Goodman Cancer Research Centre

A new breast cancer study recently published in Cell Metabolism led by Drs. Julie St-Pierre and Peter Siegel of McGill University’s Goodman Cancer Research Centre, shows that breast cancer cells that spread to the lungs do not depend on one specific pathway or fuel source, but instead rely on the ability of cancer cells to engage multiple metabolic pathways.

“Think of it as if you are travelling to a remote destination that is accessible by only one road, if this is blocked you are stuck,” explains Dr. Siegel, Associate Professor, Department of Medicine at McGill’s Faculty of Medicine. “In contrast, if you are travelling in the city and discover that your preferred route is blocked, you can adjust and take another path to your destination. That is what is happening here – if breast cancer cells are restricted to one metabolic pathway they are not able to spread as effectively as cancer cells that engage multiple pathways.”

Previous research by the team focused on metabolic regulators that led to breast cancer metastasis to the liver. In their current study, the focus shifted to how breast cancer cells metastasize to the lungs, and what metabolic pathways are used to facilitate the spread.

The findings revealed that breast cancer cells which express higher levels of the metabolic regulator known as PGC-1α are more aggressive at metastasizing to the lungs and are resistant to a certain class of drugs known as metabolic disruptors.

“Previous studies suggested that cancer cells with PGC-1α used one specific pathway to spread to the lungs. Our research indicates that not only does PGC-1α use more than one channel, but that drugs which were previously thought to block pathways used by this metabolic regulator, are not always effective,” explains Dr. Julie St-Pierre, former Associate Professor in the Department of Biochemistry at McGill who is now at the University of Ottawa.

The next step for researchers will be to determine whether cancer cells that have metastasized to other organs have changed the metabolic pathways that they use to fit the environment that they have spread to, or do they retain the same metabolic characteristics as the initial tumour.

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Funding for this research was provided by the Terry Fox Foundation, Canadian Institutes of Health Research and the Cancer Research Society

“PGC-1α Promotes Breast Cancer Metastasis and Confers Bioenergetic Flexibility against Metabolic Drugs” Sylvia Andrzejewski, , Eva Klimcakova, et al, Cell Metabolism, October 5, 2017

DOI: https://doi.org/10.1016/j.cmet.2017.09.006

October 13, 2017

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