Tyrosine Kinase Signaling in Cancer Metabolism: PKM2 Paradox in the Warburg Effect

The Warburg Effect, or aerobic glycolysis, is one of the major metabolic alterations observed in cancer. Hypothesized to increase a cell's proliferative capacity via regenerating NAD+, increasing the pool of glycolytic biosynthetic intermediates, and increasing lactate production that affects the tumor microenvironment, the Warburg Effect is important for the growth and proliferation of tumor cells. The mechanisms by which a cell acquires the Warburg Effect phenotype are regulated by the expression of numerous oncogenes, including oncogenic tyrosine kinases. Oncogenic tyrosine kinases play a significant role in phosphorylating and regulating the activity of numerous metabolic enzymes. Tyrosine phosphorylation of glycolytic enzymes increases the activities of a majority of glycolytic enzymes, thus promoting increased glycolytic rate and tumor cell proliferation. Paradoxically however, tyrosine phosphorylation of pyruvate kinase M2 isoform (PKM2) results in decreased PKM2 activity, and this decrease in PKM2 activity promotes the Warburg Effect. Furthermore, recent studies have shown that PKM2 is also able to act as a protein kinase using phosphoenolpyruvate (PEP) as a substrate to promote tumorigenesis. Therefore, numerous recent studies have investigated both the role of the classical and non-canonical activity of PKM2 in promoting the Warburg Effect and tumor growth, which raise further interesting questions. In this review, we will summarize these recent advances revealing the importance of tyrosine kinases in the regulation of the Warburg Effect as well as the role of PKM2 in the promotion of tumor growth

Materials informatics for self-assembly of functionalized organic precursors on metal surfaces

「教師なし機械学習」を用いてナノ材料開発に必要なガイドラインを作ることに成功しました. 京都大学プレスリリース. 2018-08-03.Bottom-up fabrication via on-surface molecular self-assembly is a way to create defect-free, low-dimensional nanomaterials. For bottom-up fabrication to succeed, precursor molecules which correctly assemble into the target structure must be first identified. Here we present an informatics technique which connects self-assembled structures with particular chemical properties of the precursor molecules. Application of this method produces a visual output (a dendrogram) that functions much like the periodic table, but whereas the periodic table puts atoms into categories according to the way in which they bond to each other, the dendrogram put molecules into categories according to the way in which they arrange in a self-assembled structure. By applying this method to the case of functionalized bianthracene precursors adsorbed to copper(111), we identify the functional groups needed to assemble one-dimensional chains, two-dimensional tilings, and other shapes. This methodology can therefore help to identify appropriate precursor molecules for forming target nanomaterials via bottom-up fabrication

Resonant tunneling of Hydrogen in Pd

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Atomically Resolved Surface Structure of SrTiO3(001) Thin Films Grown in Step-Flow Mode by Pulsed Laser Deposition

The surface structure of SrTiO3(001) thin films homoepitaxially grown by PLD in step-flow mode was characterized using low temperature STM. It was found that one-dimensional (1D) TiOx-based nanostructures were formed on the thin film surface and their density increased with increasing thin film thickness. Most of the 1D nanostructures disappeared after a post-deposition annealing, indicating that this structure is metastable due to the nonequilibrium growth mode. The resulting surface after annealing exhibited similar features to that of a thinner film, having a domain structure with (2x1) and (1x2) reconstructions, but with fewer oxygen-vacancy-type defects. These results imply that the step-flow growth is likely to produce TiOx-rich surface and Ti deficiencies in the film. By the post-deposition annealing, the rich TiOx would diffuse from the surface into the film to compensate defects associated with Ti vacancies and oxygen vacancies, resulting in the stable surface structure with fewer oxygen vacancies. Thus, STM measurements can provide us with a microscopic picture of surface stoichiometry of thin films originating in the dynamics of the growth process, and can present a new approach for designing functional oxide films.Comment: 12 pages, 4 figure

Two distinct surface terminations of SrVO3 (001) ultrathin films as an influential factor on metallicity

Pulsed laser deposition-grown SrVO3 (001) ultrathin films on SrTiO3 (001) substrates were investigated by in situ low-temperature scanning tunneling microscopy and spectroscopy. SrVO3 (001) ultrathin films showed two distinct surface terminations. One termination was a (√2 ×√2)-R45° reconstruction as was previously observed for SrVO3 (001) thick films, while the other was a (√5 ×√5)-R26.6° reconstruction. Scanning tunneling spectroscopy revealed that the (√2 ×√2)-R45° surface shows a metallic electronic structure, whereas the (√5×√5)-R26.6° surface exhibits a significantly reduced density of states at the Fermi level. These results suggest that the surface reconstruction may be an important factor to influence metallicity in epitaxial ultrathin films of transition metal oxides

Stripe charge ordering in SrO-terminated SrTiO3(001) surfaces

The local electronic structure of the SrO-terminated SrTiO3(001) surface was explored using scanning tunneling microscopy. At low bias voltages in the empty states, a unidirectional structure with a periodicity of 3 unit cells, superimposed on a c(2 x 2) reconstructed structure, was found to develop along the crystallographic a axis. This structure indicates a charge-ordered stripe induced by carrier doping from oxygen vacancies in the SrO and the subsurface TiO2 planes. In the filled states, localized deep in-gap states were observed in addition to large energy gaps in the tunneling spectra. This result represents inelastic tunneling due to significant electron-lattice interaction associated with unidirectional lattice distortion in the SrO-terminated surface.Comment: 6 pages, 5 figures, accepted for publication in PR