Montréal scientists identify a potential target to reduce the
progression of metastases, the main cause of death for breast cancer
MONTREAL, April 15, 2013 /CNW Telbec/ - A team of researchers at the
IRCM, led by Dr. Jean-François Côté, made an important discovery in
breast cancer, which will published online this week by the scientific
journal Proceedings of the National Academy of Sciences (PNAS). The Montréal scientists identified the DOCK1 protein as a potential
target to reduce the progression of metastases in patients suffering
from breast cancer, the most common type of cancer in women.
Dr. Côté's laboratory is interested in metastasis, which is the spread
of cancer from an organ (or part of an organ) to another. Nearly 90 per
cent of cancer patient deaths are attributable to metastasis, thus
explaining the importance of understanding the underlying cellular and
molecular mechanisms of this harmful process.
"Despite important breakthroughs in breast cancer treatment, few
mechanisms are known to explain the spread of metastases," says Dr.
Côté, Director of the Cytoskeletal Organization and Cell Migration
research unit at the IRCM. "We are looking to identify the proteins
that regulate the metastatic process so that new agents can be
developed and combined with current treatments."
Two major breast cancer subtypes, HER2+ and Basal, have a tendency to be
metastatic and recurrent, and are ultimately associated to a poor
survival rate. Research at the IRCM was conducted on the HER2+ type
(Human Epidermal growth factor Receptor 2), which represents
approximately 25 per cent of breast cancer cases. HER2 positive tumours
tend to develop and spread more quickly than other types of tumours.
"By studying a genetic mouse model with HER2+ breast cancer, we
identified the protein DOCK1 as an important regulator of metastasis,"
explains Mélanie Laurin, doctoral student in Dr. Côté's laboratory and
first author of the study. "When we eliminated this protein in mice,
our results showed a significant decrease in lung metastases. We also
discovered that the DOCK1 protein contributes to the growth of
"To show the correlation between the expression of DOCK1 and breast
cancer prognosis, we performed an analysis of several databases of
patient genic," adds Dr. Benjamin Haibe-Kains, researcher at the IRCM
who collaborated with Dr. Côté's team. "We did indeed discover that
high levels of DOCK1 in HER2+ or Basal breast cancer patients are
associated with a lower prognosis, or recurrence of the disease."
"Our work defined a new molecule required for the progression of breast
cancer to the metastatic stage and allowed us to identify new markers
that could become potential targets to stop the progression of
metastases," concludes Dr. Côté. "We also showed that a chemical
inhibitor of the DOCK1 protein, developed by Dr. Yoshinori Fukui, our
collaborator in Japan, can stop the migration of cancerous cells. These
results could eventually lead to the development of drugs that would
limit the progression of metastatic breast cancer and could thereby
improve patient prognosis."
"We are proud to fund this research," comments Melody Enguix, Scientific
Communication Advisor at the Canadian Cancer Society. "The findings are
another important step toward understanding how we can stop metastases,
which are the cause of most breast cancer deaths."
About the research project
Several researchers collaborated in this study, including Jean-François
Côté, Mélanie Laurin, Benjamin Haibe-Kains (Director of the
Bioinformatics and Computational Genomics research unit), Jennifer
Huber, Ariane Pelletier and Tarek Houalla from the IRCM; Morag Park and
William J. Muller from the Rosalind and Morris Goodman Cancer Research
Centre at McGill University; and Yoshinori Fukui from the Medical
Institute of Bioregulation at Kyushu University in Japan. Research at
the IRCM was funded by the Canadian Cancer Society and the Fonds de
recherche du Québec - Santé.
For more information on the published article, entitled Rac-specific guanine nucleotide exchange factor DOCK1 is a critical
regulator of HER2-mediated breast cancer metastasis, please refer to the PNAS website: http://www.pnas.org/.
Breast cancer statistics
According to the Canadian Cancer Society, breast cancer continues to be
the most frequently diagnosed cancer in women, with 22,700 new cases
expected in Canada in 2012, which represents approximately one-quarter
(26 per cent) of all new cancer cases in women. Breast cancer is the
second leading cause of death from cancer in Canadian women. In Quebec,
an estimated 5,500 women will be diagnosed with breast cancer and 1,350
will die of breast cancer in 2012.
About Jean-François Côté
Jean-François Côté obtained a PhD in biochemistry from McGill
University. He is Associate IRCM Research Professor and Director of the
Cytoskeletal Organization and Cell Migration research unit. Dr. Côté is
also associate research professor in the Department of Medicine
(accreditation in molecular biology) at the Université de Montréal, and
adjunct professor in the Department of Medicine (Division of
Experimental Medicine) at McGill University. He is a Research Scholar
from the Fonds de recherche du Québec - Santé. For more information,
About the IRCM
Founded in 1967, the Institut de recherches cliniques de Montréal (www.ircm.qc.ca) is currently comprised of 35 research units in various fields, namely
immunity and viral infections, cardiovascular and metabolic diseases,
cancer, neurobiology and development, systems biology and medicinal
chemistry. It also houses three specialized research clinics, eight
core facilities and three research platforms with state-of-the-art
equipment. The IRCM employs 425 people and is an independent
institution affiliated with the Université de Montréal. The IRCM Clinic
is associated to the Centre hospitalier de l'Université de Montréal
(CHUM). The IRCM also maintains a long-standing association with McGill
University. The IRCM is funded, in part, by the Quebec ministry of
Higher Education, Research, Science and Technology.
SOURCE: Institut de recherches cliniques de Montréal
For further information:
For more information and to schedule an interview with Dr. Côté, please contact:
Communications Officer (IRCM)
Communications Director (IRCM)