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. 2018 Oct 8;28(11):1090–1102. doi: 10.1038/s41422-018-0086-7

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — PKM2 is a critical mediator of cellular resistance to DNA-damaging treatment. a Clonogenic survival of U87 shCtrl and shPKM2 cells following irradiation with 0 to 8 Gy. Western blot (inset) shows PKM2 expression in these cells. Results are mean ± SE (n = 3). *P < 0.05. b Clonogenic survival of U87 cells treated with control siRNA or siRNA targeting PKM1 or PKM2 24 h prior to irradiation. Western blot (inset) demonstrates PKM1 and PKM2 expression 24 h after siRNA treatment. Cells were irradiated as indicated. Results are mean ± SE (n = 4). *P < 0.05. c Mice bearing U87 tumors expressing shCtrl or shPKM2 were assigned to no radiation or radiation treatment (2 Gy × 5 d) groups. The average volume for shCtrl tumors was 132.5 mm³ at the start of treatment; for shPKM2 tumors, the average volume at the start of treatment was 137.7 mm³. shCtrl tumor reached target volume to begin treatment in 36.5 days on average while shPKM2 tumors required 44.8 days to reach the target volume. Tumor growth was monitored for 24 d. Results are mean tumor volume relative to starting volume ± SD (6 mice/group). *P < 0.05. d MRI images of a representative intracranial U87/EGFRvIII tumor at day 8 (upper left panel) and 15 (upper right panel). H&E (middle and lower left panels) and Ki-67 (middle and lower right panels) staining of a day 15 tumor. e Mice were implanted with 50,000 U87/EGFRvIII cells expressing shCtrl or shPKM2 by intracranial injection and assigned to no radiation or radiation treatment (4 Gy × 3 d) groups (see Table for details). Mean survival for each group was calculated and survival was analyzed by the Kaplan Meier method, with comparisons between the groups made by a log rank test (see Table). P < 0.05 was considered significant. f Patients receiving genotoxic treatment in the TCGA GBM cohort were stratified by PKM expression (PKM High = upper 10th percentile; PKM Low = lower 90th percentile) and overall survival was analyzed by the Kaplan Meier method (P = 0.006 for the difference between high and low expression groups)