Cancer cells can fail in cytokinesis leading to tetraploidy and chromosomal instability, a common phenotype of malignant cells. Our lab is interested in understating the causes of cytokinesis failure in cancer cells.
A key regulator of the process of cytokinesis is the enzyme Aurora B kinase. Aurora B is over-expressed in a variety of tumor tissues and Aurora B inhibitors are currently in clinical trials as potential chemotherapeutic agents. Interestingly, dys-regulation of Aurora B is known to cause cytokinesis failure and tetraploidization. However, the mechanism of Aurora B mediated tetraploidization is not yet known.
An essential step in cytokinesis is phosphorylation of myosin regulatory light chain (MLC), required for actin–myosin interaction and formation of the cleavage furrow and myosin light chain kinase (MLCK) is a key enzyme that phosphorylates MLC during cytokinesis. Previous studies from our lab have shown that cancer cells fail in cytokinesis due to deficient phosphorylation of MLC and inhibition of MLCK. Our recent studies indicate that over-expression of Aurora B is the cause of MLCK deficiency and cytokinesis failure in cancer cells. Chromosome segregation errors such as anaphase bridges can cause cytokinesis failure. Our current focus is on understanding the role of anaphase bridges in Aurora B activation, MLCK and MLC inhibition and cytokinesis failure.