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Shinoda, K.

Publications and source records attributed to Shinoda, K..

2 recordsLinked to original sources
bioRxiv2018

A new lipid force field (FUJI)

To explore inhomogeneous and anisotropic systems such as lipid bilayers, the Lennard-Jones particle mesh Ewald (LJ-PME) method was applied without a traditional isotropic dispersion correction. As the popular AMBER and CHARMM lipid force fields were developed using a cutoff scheme, their lipid bilayers unacceptably shrank when using LJ-PME method. A new lipid force field (FUJI) was developed on the basis of the AMBER force field scheme including the Lipid14 van der Waals parameters. Point charges were calculated by the restrained electrostatic potentials of many lipid conformers. The torsion energy profiles were calculated by high level ab initio molecular orbitals (LCCSD(T)/Aug-cc-pVTZ//LMP2/Aug-cc-pVTZ); then, the molecular mechanical dihedral parameters were derived by means of a fast Fourier transform. Incorporating these parameters into a new lipid force field without any fittings to experimental data, desirable lipid characteristics such as the area per lipid and lateral diffusion coefficients were obtained by GROMACS molecular dynamics simulations using the LJ-PME method and hydrogen virtual sites. The stability and structures of large membranes with undulatory fluctuations were studied by a multidrug efflux transporter (AcrABZ-TolC) with inner and outer membranes.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC=\"FIGDIR/small/373183_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (92K):\norg.highwire.dtl.DTLVardef@12cf574org.highwire.dtl.DTLVardef@a6cdbforg.highwire.dtl.DTLVardef@10dbd16org.highwire.dtl.DTLVardef@f8fd3a_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗
bioRxiv2018

Tumor cell-adipocyte gap junctions activate lipolysis and are essential for breast tumorigenesis

A pro-tumorigenic role for adipocytes has been identified in breast cancer, and reliance on fatty acid catabolism found in aggressive tumors. The molecular mechanisms by which tumor cells coopt neighboring adipocytes, however, remain elusive. Here, we describe a direct interaction linking tumorigenesis to adjacent adipocytes. We examine breast tumors and their normal adjacent tissue from several patient cohorts, patient-derived xenografts and mouse models, and find that lipolysis and lipolytic signaling are activated in neighboring adipose tissue. We find that functional gap junctions form between breast cancer cells and adipocytes. As a result, cAMP is transferred from breast cancer cells to adipocytes and activates lipolysis in a gap junction-dependent manner. We identify connexin 31 (GJB3), which promotes receptor triple negative breast cancer growth and activation of lipolysis in vivo. Thus, direct tumor cell-adipocyte interaction contributes to tumorigenesis and may serve as a new therapeutic target in breast cancer. One sentence summaryGap junctions between breast cancer cells and adipocytes transfer cAMP and activate lipolysis in the breast tumor microenvironment to support growth.

cancer biology↗