Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac signaling

In the absence of Tara, Trio binds to E-cadherin and increases activation of the E-cadherin transcriptional repressor Tbx3

Proteasomal degradation of polycomb-group protein CBX6 confers MMP-2 expression essential for mesothelioma invasion.

金沢大学がん進展制御研究所The aggressive invasiveness of malignant mesothelioma limits cancer therapy, however, the molecular mechanisms underlying the invasiveness remain largely unknown. Here we found that the matrix metalloproteinase-2 (MMP-2) was required for the invasion of mesothelioma cells in the collagen matrix and the gene expression of MMP-2 was correlated with the invasive phenotype. The MMP-2 gene expression was regulated by DNA and histone methylation around the transcription start site, implicating the involvement of the polycomb repressive complex (PRC). Knockdown of PRC component chromobox 6 (CBX6) promoted MMP-2 expression and invasion of mesothelioma cells. Transcriptome analysis suggested that CBX6 regulates sets of genes involved in cancer cell migration and metastasis. In invasive but not non-invasive cells, CBX6 was constantly unstable owing to ubiquitination and protein degradation. In human tissues, CBX6 localized in the nuclei of normal mesothelium and benign mesothelioma, but the nuclear staining of CBX6 was lost in malignant mesothelioma. These results suggest involvement of proteasomal degradation of CBX6 in mesothelioma progression.This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article\u27s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article\u27s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/

Peptidoglycan recognition protein (PGRP)-LE and PGRP-LC act synergistically in Drosophila immunity

In innate immunity, pattern recognition molecules recognize cell wall components of microorganisms and activate subsequent immune responses, such as the induction of antimicrobial peptides and melanization in Drosophila. The diaminopimelic acid (DAP)-type peptidoglycan potently activates imd-dependent induction of antibacterial peptides. Peptidoglycan recognition protein (PGRP) family members act as pattern recognition molecules. PGRP-LC loss-of-function mutations affect the imd-dependent induction of antibacterial peptides and resistance to Gram-negative bacteria, whereas PGRP-LE binds to the DAP-type peptidoglycan, and a gain-of-function mutation induces constitutive activation of both the imd pathway and melanization. Here, we generated PGRP-LE null mutants and report that PGRP-LE functions synergistically with PGRP-LC in producing resistance to Escherichia coli and Bacillus megaterium infections, which have the DAP-type peptidoglycan. Consistent with this, PGRP-LE acts both upstream and in parallel with PGRP-LC in the imd pathway, and is required for infection-dependent activation of melanization in Drosophila. A role for PGRP-LE in the epithelial induction of antimicrobial peptides is also suggested

Safe Resection of Renal Cell Carcinoma with Liver Invasion Using Liver Hanging Technique Supported by Preoperative Portal Vein Embolization

In cases of RCC with liver involvement, partial hepatectomy is known to provide a better chance of survival for patients. For this reason, complete resection with clear surgical margin is thought to be necessary to achieve favorable outcome. Anterior liver hanging maneuver was extremely useful during hemihepatectomy in this rare type of RCC. A 63-year-old male was diagnosed with a large right renal cell carcinoma. The tumor measured 10 cm in diameter with tumor thrombus toward the inferior vena cava (IVC). In addition, we observed direct infiltration to the liver. We attempted a preoperative portal vein embolization (PVE) to preserve residual liver volume and function after right lobectomy. After PVE the resected volume decreased from 921 cm3 (71%) to 599 cm3 (53.4%). During the procedure, a nasogastric tube was placed in the retrohepatic space for liver hanging maneuver according to the original Belghiti’s maneuver after dissection of the renal artery and vein. After hepatic parenchymal transection exposing vena cava, the right hepatic veins were safely transected using vascular stapler; right nephrectomy and hemihepatectomy were performed. The patient recovered without postoperative hepatic or urinary complications and has remained free of local recurrence and any de novo metastasis for 18 months