'Grow or Go' Switch

Researchers discover brain tumor mechanism

E Antonio ChioccaSean LawlerResearchers at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James) have discovered a mechanism that regulates the behavior of glioblastoma multiforme cells.

Cancer cells in rapidly growing brain tumors must adapt to periods of energy fluctuation. When glucose levels are high, tumor cells grow and proliferate; when levels are low, the cells grow less and migrate more.

Researchers discovered that the microRNA miR-451 coordinates this “grow-or-go” behavior.

“We found that glioblastoma cells use miR451 to sense glucose availability,” says co-author E. Antonio Chiocca, MD, PhD, professor and chair of Neurological Surgery, and co-leader of the OSUCCC – James Viral Oncology Program. “Levels of miR451 directly shut down the engine of the tumor cell if there is no glucose, or rev it up if glucose is plentiful. This suggests that this molecule might be a useful biomarker to predict a glioblastoma patient’s prognosis. It also might be used as a target to develop drugs to fight these tumors.”

“The change in miR-451 expression enabled the cells to survive periods of stress caused by low glucose, and it caused them to move, perhaps enabling them to find a better glucose supply,” says principal investigator Sean Lawler, PhD, assistant professor of Neurological Surgery. “The migration of cancer cells from the primary tumor, either as single cells or chains of cells, into the surrounding brain is a problem with these tumors. By targeting miR-451, we might limit the tumor’s spread and extend a patient’s life.”

Published in the journal Molecular Cell.

Grow or Go Switch-2

Kaplan-Meier plot showing that high miR-451 expression is associated with poorer survival in patients with glioblastoma multiforme. The plot was generated using data obtained from The Cancer Genome Atlas. (p = 0.036) Reprinted from Molecular Cell, 37:620, Godlewski J., Nowicki M.O., Bronisz A., et al. MicroRNA-451 Regulates LKB1/AMPK Signaling and Allows Adaptation to Metabolic Stress in Glioma Cells.

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