By Martin Primeau
Jean-Claude Labbé’s research team at the IRIC published a study that suggests why certain anti-cancer drugs have variable effectiveness depending on the type of cancer. The results of this research were recently published in the journal Molecular Biology of the Cell.
The researchers were interested in a cellular quality-control system called “spindle assembly checkpoint”, or more simply the SAC. This regulatory system prevents a cell from dividing as long as the chromosomes are not properly aligned at the center of the cell, thus preventing errors during cell division.
Cancer cells often bypass the SAC and divide abnormally. Anti-mitotic drugs slow this process by relying on the effectiveness of the SAC but treatments do not always have the same outcome, and the IRIC researchers wanted to know why.
To achieve this, they scrutinized the division of embryonic cells from an animal model commonly used in research: the nematode worm Caenorhabditis elegans.
The researchers discovered that the strength of the SAC varies depending on cell type.
In certain cells, such as those that eventually become the reproductive cells, the SAC is a vigilant gatekeeper and delays cell division when chromosome alignment is disrupted. In cells destined to give rise to other cell types, the SAC is less attentive and is unable to delay cell division for as long. This presumably means that chromosome segregation errors are more likely to occur.
Since the mechanisms of cell division, just like the genes involved, are relatively similar in humans and worms, researchers think they have found a possible mechanism to explain why some drugs work better for certain cancers, thus paving the way for the development of more targeted antimitotic drugs. Understanding the mechanisms governing the relationship between the SAC and cell fate is therefore important from both a fundamental and a clinical point of view.
To read the full article : https://doi.org/10.1091/mbc.E18-04-0215
The embryo of the nematode Caenorhabditis elegans undergoes asymmetric divisions to generate the cells that eventually become the reproductive cells (germline P cells, coloured in red). The strength of the SAC increases as cell size decreases, yet this increase in SAC strength is more pronounced in germline P cells than in somatic cells.
Spindle assembly checkpoint strength is linked to cell fate in the Caenorhabditis elegans embryo.
R. Gerhold A, Poupart V, Labbé J-C, S. Maddox P
Molecular Biology of the Cell; Vol. 29, No. 12