Fig. 8.

PKM2-H2Bub1 axis regulates tumor cell growth. a Equal amounts (5 × 10⁴) of H1299 cells transfected with GFP-tagged wild-type H2B combined with control shRNA (H2BWT + shCont.), GFP-tagged wild-type H2B together with PKM2-specific shRNA (H2BWT + shPKM2), or GFP-tagged K120R-mutated H2B together with PKM2-specific shRNA (H2BK120R + shPKM2) were plated and counted continuously for 4 days (left). Equal amounts (5 × 10⁴) of H1299 cells transfected with control siRNA (siCont.), PKM2-specific siRNA (siPKM2), or siPKM2 together with RNF20-specific siRNA (siPKM2 + siRNF20) were plated and counted continuously for 4 days (right). The results are shown as mean ± S.D. b In vivo tumor growth analysis was performed with H1299 cells stably transfected with GFP-tagged wild-type H2B combined with control shRNA (shCont. + H2BWT), GFP-tagged wild-type H2B together with PKM2-specific shRNA (shPKM2 + H2BWT), or GFP-tagged K120R-mutated H2B together with PKM2-specific shRNA (shPKM2 + H2BK120R) in nude mice. n = 7 mice in each group. Tumor weights are shown (right, one column only represents the weight of one tumor). c IHC staining with the indicated antibodies was performed on 75 pairs of nonsmall cell lung cancer specimens. Representative photos are shown, and quantification data is shown on the left. d IF (n = 4) and western blot (n = 8) analyses with the indicated antibodies were performed on 12 pairs of breast cancer specimens. Representative photos of IF staining and western blot are shown. e Working model. In addition to the canonical pathway of PKM2 in the regulation of the Warburg effect through functioning as a rate-limiting enzyme of glycolysis, our work demonstrates that a H2Bub1-mediated epigenetic pathway is also employed by PKM2 to control reprogrammed energy metabolism during cancer development