PARP14 promotes the warburg effect in hepatocellular carcinoma by inhibiting JNK1-dependent PKM2 phosphorylation and activation

Most tumour cells use aerobic glycolysis (the Warburg effect) to support anabolic growth and evade apoptosis. Intriguingly, the molecular mechanisms that link the Warburg effect with the suppression of apoptosis are not well understood. In this study, using loss-of-function studies in vitro and in vivo, we show that the anti-apoptotic protein poly(ADP-ribose) polymerase (PARP)14 promotes aerobic glycolysis in human hepatocellular carcinoma (HCC) by maintaining low activity of the pyruvate kinase M2 isoform (PKM2), a key regulator of the Warburg effect. Notably, PARP14 is highly expressed in HCC primary tumours and associated with poor patient prognosis. Mechanistically, PARP14 inhibits the pro-apoptotic kinase JNK1, which results in the activation of PKM2 through phosphorylation of Thr365. Moreover, targeting PARP14 enhances the sensitization of HCC cells to anti-HCC agents. Our findings indicate that the PARP14-JNK1-PKM2 regulatory axis is an important determinant for the Warburg effect in tumour cells and provide a mechanistic link between apoptosis and metabolism

All-depth dispersion cancellation in spectral domain optical coherence tomography using numerical intensity correlations

In ultra-high resolution (UHR-) optical coherence tomography (OCT) group velocity dispersion (GVD) must be corrected for in order to approach the theoretical resolution limit. One approach promises not only compensation, but complete annihilation of even order dispersion effects, and that at all sample depths. This approach has hitherto been demonstrated with an experimentally demanding ‘balanced detection’ configuration based on using two detectors. We demonstrate intensity correlation (IC) OCT using a conventional spectral domain (SD) UHR-OCT system with a single detector. IC-SD-OCT configurations exhibit cross term ghost images and a reduced axial range, half of that of conventional SD-OCT. We demonstrate that both shortcomings can be removed by applying a generic artefact reduction algorithm and using analytic interferograms. We show the superiority of IC-SD-OCT compared to conventional SD-OCT by showing how IC-SD-OCT is able to image spatial structures behind a strongly dispersive silicon wafer. Finally, we question the resolution enhancement of 2–? that IC-SD-OCT is often believed to have compared to SD-OCT. We show that this is simply the effect of squaring the reflectivity profile as a natural result of processing the product of two intensity spectra instead of a single spectrum