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Research Highlight | January 15, 2020

Study provides new insights on how aggressive breast cancer cells get the energy they need to grow

It’s well understood that cancer cells need more energy than normal cells to grow and spread, but scientists are still struggling to determine the mechanisms they use to get this extra energy.

Now, a study by a team of TFRI-funded researchers published in Nature Communications (July 2019) is providing some insights into these mechanisms, revealing, for example, how cells from an aggressive type of breast cancer – HER2-positive breast cancer – hijack metabolic pathways to produce the extra energy they need to grow and spread.

It all begins with a protein kinase known as c-Src, explains Dr. Harvey Smith, a research associate at the Goodman Cancer Research Centre (McGill University in Montreal) and the paper’s first author. According to Dr. Smith, the activation of this kinase (which occurs frequently in HER2-positive breast cancers – nearly 20 per cent of all cases) increases energy generation within the cancer cell. This not only helps to fuel the cells’ growth, but also results in the production of a protein complex called PRC2, which is also known to play a role in cancer by silencing gene activity, part of an overall gene regulation process referred to as epigenetics.

These findings not only help to explain the biological processes used by these aggressive breast cancer cells to get extra energy, but also identify a new link between cellular energy generation and epigenetics and reveal a potential therapeutic target that could bring new hope to some patients with this disease.

“Right now, there are drugs being tested in clinical trials that target a protein called EZH2, which is one of the proteins that makes up the PRC2 complex,” says Dr. Smith. “Based on these findings and our other recently published data, we are currently exploring avenues for clinical translation involving the use of EZH2 inhibitors in HER2-positive breast cancer patients, particularly those whose tumours fail to respond to standard-of-care regimens targeting HER2.”

 

Study

An ErbB2/c-Src axis links bioenergetics with PRC2 translation to drive epigenetic reprogramming and mammary tumorigenesis

Authors

Harvey W. Smith, Alison Hirukawa, Virginie Sanguin-Gendreau, Ipshita Nandi, Catherine R. Dufour, Dongmei Zuo, Kristofferson Tandoc, Matthew Leibovitch, Salendra Singh, Jonathan P. Rennhack, Matthew Swiatnicki, Cynthia Lavoie, Vasilios Papavasiliou, Carolin Temps, Neil O. Carragher, Asier Unciti-Broceta, Paul Savage, Mark Basik, Vincent van Hoef, Ola Larsson, Caroline L. Cooper, Ana Cristina Vargas Calderon, Jane Beith, Ewan Millar, Christina Selinger, Vincent Giguère, Morag Park, Lyndsay N. Harris, Vinay Varadan, Eran R. Andrechek, Sandra A. O’Toole, Ivan Topisirovic & William J. Muller 

Funding

This study is partially funded by a Terry Fox New Frontiers Program Project Grant in Targeting Metabolic Vulnerabilities in Cancer