Mitosis in the spotlight: Another step to new therapies for uncontrolled cell division

A team of researchers from IBMC published a study this week in the online edition of the journal Nature Cell Biology that is capturing interest within the scientific community, by exploring a means to new therapies for uncontrolled cell division, as in the case of cancer.
The study proves that certain proteins, such as CLASPs, may be used as targets to make cancer cells unviable during cell division. The team behind the project, led by Helder Maiato, was recently awarded a Pfizer award for Basic Research.
Normally, during cell division the genetic material, condensed in chromosomes, divides itself equally to the two poles defined by a division axis, constituting the mitotic spindle. At each of these poles a daughter cell will be reorganized, and each will contain the same genetic information as the original cell. According to Elsa Logarinho, one of the authors of this work, “it is very important that this spindle is formed correctly and maintains its bipolar shape” since it is this that ensures equal “division of the chromosomes between the two daughter cells,” she adds.
 
However, in some cases, and for various reasons, the mitotic spindle acquires a multipolar structure, resulting in an unequal distribution of the genetic material. Frequently, in multipolar divisions, which are  a hallmark of various types of cancer, cells “evade” the control mechanisms and are able to cluster the various poles into a bipolar spindle, allowing the survival and transmission of the cancer genome.

 
The study now published shows that CLASPs are involved in the structuring of the mitotic spindle during cell division. The authors show that when the function of CLASPs is affected, it limits the ability of cancer cells to regroup the multiple poles into a bipolar spindle, making the process irreversible. In this case, the cancerous daughter cells cannot survive. Because of this, “in theory, if we devise ways to target CLASPs only in cancercells, for example, we can prevent tumours from continuing growth”, says Helder Maiato.

Another important discovery of this research is the finding that chromosomes themselves can influence the type of mitotic spindle that forms. Before the separation into the daughter cells, the chromosomes must be aligned in the cell equator, a process that involves molecular ‘motors’. What the IBMC team demonstrated was that  ‘motors’ located within the chromosomes themselves, which impact on the mitotic spindle during this alignment process, can cause irreversible fragmentation of the poles. This change in paradigm establishes the chromosomes not as passive bodies, but instead as active players involved in determining the structure of the mitotic spindle.