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Cancer-promoting protein is vital to safe division of tumor cells
Date:12/6/2013

HOUSTON Researchers have caught a protein they previously implicated in a variety of cancer-promoting roles performing a vital function in cell division, survival and development of brain tumors.

In a paper published in Molecular Cell, Zhimin Lu, Ph.D., professor of Neuro-Oncology at The University of Texas MD Anderson Cancer Center and colleagues report how a tumor-specific protein flips a crucial switch in an irregular mechanism for mitosis that allows cancer cells to safely divide.

"Our research shows that tumor cells rely heavily on a distinct mechanism for orderly cell division that's driven by oncogene-induced pyruvate kinase M2," Lu said.

After a cell begins division by replicating all of its chromosomes, mitosis separates them into two identical sets of chromosomes for both cells. After mitosis, cytokinesis completes cell divison.

"Without PKM2 regulating a checkpoint in mitosis, the tumor cell would not successfully divide," Lu said. "Depleting PKM2 led to an uneven distribution of DNA to the two new cells, triggering programmed cell death, or apoptosis, of those cells after division."

"This new, additional role for PKM2 in cancer development and survival may provide a molecular basis for diagnosing and treating tumors with upregulated PKM2," Lu said. He and his colleagues have now identified four specific mechanisms by which PKM2 promotes cancer development.

PKM2 regulation of mitosis worsens tumors in mice; affects human glioblastoma

The key relationship between PKM2 activity and mitosis uncovered by the researchers led to rapid brain tumor growth when activated in mice, while blocking it reduced tumor volume by 83 percent and more than doubled survival from about 20 days to beyond 40 days.

Analysis of 50 human glioblastoma multiforme tumors and 50 lung cancer tumors confirmed the relationship in human cancer and indicated an effect on survival for patients with
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Contact: Scott Merville
SMerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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