A new study led by University of Texas MD Anderson Cancer Center researchers entitled “PKM2 phosphorylates MLC2 and regulates cytokinesis of tumor cells” shows that the pyruvate kinase M2 controls cell division — a finding with clear implications for tumor growth biology and therapeutics. The study was published in the journal Nature Communications.
Pyruvate kinase M2 (PKM2) is highly expressed in tumors and a key factor for cell growth; however, whether or not it controls cell division was still unknown. In this new research, a team of researchers at MD Anderson led by Zhimin Lu, M.D., Ph.D., professor of neuro-oncology studied the role of PKM2 in cell division using brain tumor development in mice as a model. They found that PKM2 interacts with myosin light chain 2 ( MLC2), a motor protein, that is responsible for separating two cells in the process of cell division. Specifically, the authors found that in brain tumors, PKM2 induces MCL2 phosphorylation, required for its process in the division of parental and daughter cells, a process known as cytokinesis.
Dr. Lu noted, “PKM2 is expressed at high levels during tumor progression and is important for cell growth. However, there’s been little information about whether it directly controls cell division. Our findings underscored its function in tumor formation during the final stages of cell division known as cytokinesis. The results revealed that PKM2-regulated MLC2 phosphorylation, and the related cytokinesis are instrumental in brain tumor development and are found to control preciselycell division. More importantly, our research shows that PKM2-regulated cytokinesis occurs in malignant tumors with a bad outcome, such as glioblastoma, pancreatic cancer, and melanoma.”
Additionally, the authors report that PKM2 regulating MLC2 phosphorylation and activation is enhanced by genes that are commonly found mutated in tumors, such as EGFR, K-Ras and B-Raf. Thus, these findings demonstrate PKM2 as a new factor leading to cell cycle progression and part of the tumors’ mechanistic to control and promote tumorigenesis. With better understanding of how tumors grow, next-generation therapeutics can be designed to counteract tumor growth mechanisms.