One in eight women will develop breast cancer during their lifetime. Unfortunately, men are not safe either. Nowadays, it is possible to cure breast cancer with many treatments, but unfortunately, some types of breast cancer are more aggressive than others and are therefore more difficult to treat. This is why our research team in Dr. Catherine Mounier’s lab, (UQAM, Montreal) focuses on a type of cancer called triple negative breast cancer (TNBC), known to be very aggressive and more difficult to treat. TNBC is a type of breast cancer that does not have any of the receptors that are commonly found in breast cancer. If you compare the cancer cells to a house, to enter there is a front door and this door has locks. In breast cancer cells, the doors have 3 kinds of locks, called receptors. The first lock is the for the hormone estrogen, the second for the hormone progesterone, and the last is a protein called human epidermal growth factor (HER2). If the cancer has any of these three locks, doctors have a few keys (like hormone therapy or other drugs) they can use to help destroy the cancer cells. However, if you have triple-negative breast cancer, it means those three locks aren’t there, so doctors have fewer keys for treatment.
The goal of our research was to find a new treatment target. This target would end up being a protein called SCD1 (Stearoyl-co-desaturase-1). SCD1 is a protein that helps the formation of saturated fatty acids such as palmitoleate and oleate. Oleate is the major product of SCD1 and is well known because it the principal ingredient in olive oil. These fatty acids have mechanistic functions in the cells and can regulate metabolism and modulate chronic metabolic diseases. From past studies, we know that SCD1 is more abundant in cancer cells compared to normal cells.
A main finding of our work was demonstrating that when we blocked SCD1 action with specific inhibitors, we were able to reduce the migration and proliferation of breast cancer cells.
In cancer, we usually measuring migration and proliferation as a marker of cancer growth. In fact, cancer initially starts as an abnormal cell which becomes immortal and multiplies rapidly and anarchically. A mass of cells then appears, becoming what we call a tumor. This tumor gradually grows and compress neighboring structures. After a while, it runs out of space. From there, the tumour continues to multiply and will therefore send cells throughout the body to invade other organs; these migrating cancer cells become metastases. To understand this process in the laboratory, we filmed the path of live cells under the microscope for a few days. Then we analyzed the films to determine the speed of multiplication and movement of the cells following administration of different treatments (like an inhibitor of SCD1, or oleate treatment). We observed that oleate, the main product of SCD1, increased cell proliferation, migration, and invasion, while the SCD1 inhibitor did the exact opposite.
In summary, we found that if cells have increased activity of SCD1, cells will metastasize, and the cancer will migrate from the breast to invade other organs. However, if SCD1 is inhibited, breast cancer cells will move, migrate, and proliferate less and consequently, the cancer will not metastasize as much as before. With these results, we can now move forward with pre-clinical models using mice, and, if SCD1 is found to be overexpressed in breast cancer cells, we can use it as a specific target for a treatment. This advance could be applicable in several other diseases where SCD1 is involved, such as other cancers or obesity.
References:
Marine Lingrand, Simon Lalonde, Antoine Jutras-Carignan, Karl-F Bergeron, Eric Rassart, Catherine Mounier
SCD1 activity promotes cell migration via a PLD-mTOR pathway in the MDA-MB-231 triple-negative breast cancer cell line.
Biological Sciences Department, Université du Québec à Montréal (UQAM), Montréal, QC H3P 3P8, Canada
Breast Cancer, 2020, DOI: 10.1007/s12282-020-01053-8, 2
Zhiqiang Guo, Karl-F Bergeron, Marine Lingrand, Catherine Mounier
Unveiling the MUFA–Cancer Connection: Insights from Endogenous and ExogenousPerspectives.
Biological Sciences Department, Université du Québec à Montréal (UQAM), Montréal, QC H3P 3P8, Canada
Int. J. Mol. Sci. 2023, 24(12), 9921; https://doi.org/10.3390/ijms24129921
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