title: Activation of Akt protects cancer cells from growth inhibition induced by PKM2 knockdown.
abstract: BACKGROUND
  PKM2 is an attractive target for cancer therapy, however, for many cancer cells, PKM2 knockdown only leads to a modest impairment of survival and proliferation. It is not known whether PKM2 knockdown rewires cell signaling pathways in these "PKM2 knockdown resistant" cells, and whether the rewired pathways are needed for their survival.
  
  
  RESULTS
  In present study, we investigated the effects of PKM2 knockdown on cellular signaling pathways in "PKM2 knockdown resistant" cancer cells. We found that knockdown of PKM2 leads to activation of Akt. Furthermore, we revealed that activation of Akt in PKM2 knockdown cells is a result of glycolysis disruption. Inhibiton of PI3K-Akt signaling pathway leads to significant growth inhibition and apoptosis in PKM2 knockdown cells.
  
  
  CONCLUSIONS
  Overall, our results indicate that activation of Akt is necessary for the survival of PKM2 knockdown cells. Combing PKM2 knockdown with PI3K or Akt inhibitors may lead to a better chance to kill tumors. Our research may provide an unexpected opportunity for the development and implementation of drugs targeting cell metabolism and aberrant Akt signaling.
authors.affiliation: School of Life Science, Lanzhou University, Lanzhou, Gansu 730000, P. R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Qin
authors.affiliation: School of Life Science, Lanzhou University, Lanzhou, Gansu 730000, P. R. China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Du
authors.affiliation: School of Life Science, Lanzhou University, Lanzhou, Gansu 730000, P. R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Engineering Science, Muskingum University, 163 Stormont St, New Concord, OH 43762, USA.
authors.forename: Wuyan
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Biomedical Science and Institutes of Molecule Medicine, Huaqiao University, Xiamen, Fujian 361021, P. R. China.
authors.forename: Jinghong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Life Science, Lanzhou University, Lanzhou, Gansu 730000, P. R. China ; Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland OH 44195, USA.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Yang
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