Death-associated proliferation kinetic in normal and transformed cells.

Pyruvate kinase M2 (PKM2) may occur in both a tetrameric and a dimeric form. When the majority of PKM2 molecules are in the highly active tetrameric conformation, glucose is primarily degraded to pyruvate and lactate with the regeneration of energy. A tumor suppressor protein, death-associated protein kinase (DAPK), interacts with PKM2 protein and stabilizes PKM2 in its active tetrameric form in normal proliferating cells. However, DAPK is widely inactivated in cancer cells, leading to the loss of the active conformation of PKM2. This may render PKM2 sensitive to cellular oxidants, switching the enzyme into its inactive dimeric form. Consequently, inhibition of PKM2 after oxidative stress contributes optimal tumor growth and allows cancer cells to withstand oxidative stress.