Novel regulatory mechanism for cell division found
BY Ron Gilmore
December 09, 2014
Medically Reviewed | Last reviewed by an MD Anderson Cancer Center medical professional on December 09, 2014
A protein kinase or enzyme known as PKM2 has proven to control cell division, potentially providing a molecular basis for tumor diagnosis and treatment.
A study, led by professor of Neuro-oncology at MD Anderson Cancer Center, showcased the non-metabolic abilities of PKM2 (pyruvate kinase M2) in promoting tumor cell proliferation when cells produce more of the enzyme.
The study results were recently published in .
Lu¡¯s group previously demonstrated that PKM2 controls gene expression by binding to transcriptional factors and phosphorylating histone, proteins that have the unique ability to turn genes on and off. Phosphorylation is a process by which a phosphate group is added to a protein.
¡°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.¡± said Lu. ¡°Our findings underscored its function in tumor formation during the final stages of cell division known as cytokinesis.¡±
Understanding how cytokinesis goes awry is important because abnormal cell division impacts tumor cell growth and spread. Lu¡¯s team looked at the role of PKM2 in brain tumor development in mice. After analyzing the protein-coding gene, MLC2 (myosin light chain 2), Lu¡¯s group revealed how phosphorylation of MLC2 by PKM2 in brain tumors occurs. Phosphorylation of MLC2 controls a process that allows separation of a dividing parental cell into two ¡®daughter¡¯ cells.
¡°The results revealed that PKM2-regulated MLC2 phosphorylation and the related cytokinesis are instrumental in brain tumor development and are found to precisely control cell division,¡± said Lu. ¡°More importantly, our research shows that PKM2-regulated cytokinesis occurs in malignant tumors with bad outcomes, such as glioblastoma, pancreatic cancer and melanoma.¡±
Tumor cells, in which certain protein-coding genes (EGFR, K-Ras and B-Raf) are activated, develop new patterns of ¡°molecular signatures¡± for regulating cell proliferation. These changes enable the tumor cells to coordinate their metabolism and cycle progression through PKM2.