bims-stacyt Biomed News
on Paracrine crosstalk between cancer and the organism
Issue of 2019‒08‒11
two papers selected by
Cristina Muñoz Pinedo
L’Institut d’Investigació Biomèdica de Bellvitge
  1. Amino Acid Biosynthesis Regulation during Endoplasmic Reticulum Stress Is Coupled to Protein Expression Demands.
  2. Interleukin-8/β-catenin mediates epithelial-mesenchymal transition in ameloblastoma.
  1. iScience. 2019 Jul 19. pii: S2589-0042(19)30247-0. [Epub ahead of print]19 204-213
    Amino Acid Biosynthesis Regulation during Endoplasmic Reticulum Stress Is Coupled to Protein Expression Demands.
    Nir Gonen, Anatoly Meller, Niv Sabath, Reut Shalgi.
      The endoplasmic reticulum (ER) stress response, also known as the unfolded protein response (UPR), is a complex cellular response to ER protein misfolding that involves transcriptional regulatory branches and a PERK-mediated translational regulatory branch. Here we revealed that amino acid biosynthesis regulation is coupled to protein synthesis demands during ER stress. Specifically, we demonstrated that the UPR leads to PERK-dependent induction in the biosynthesis of specific amino acids, and to upregulation of their corresponding tRNA synthetases. Furthermore, we found that sequences of UPR-upregulated proteins are significantly enriched with these UPR-induced amino acids. Interestingly, whereas the UPR leads to repression of ER target proteins, we showed that secreted proteins tended to escape this repression and were highly enriched for the UPR-induced amino acids. Our results unravel coordination between amino acid supply, namely, biosynthesis and tRNA loading, and demand from UPR-induced proteins under ER stress, thus revealing an additional regulatory layer of protein synthesis.
    Keywords:  Cell Biology; Expression Study; Membrane System; Transcriptomics
    DOI:  https://doi.org/10.1016/j.isci.2019.07.022
  2. Oral Dis. 2019 Aug 09.
    Interleukin-8/β-catenin mediates epithelial-mesenchymal transition in ameloblastoma.
    Jie Zhang, Yanhui Wang, Cunhui Fan, Ximei Xiao, Qian Zhang, Tao Xu, Chunmiao Jiang.
      OBJECTIVE: Epithelial-mesenchymal transition (EMT) is important in the tooth development and tumor invasion. We investigated the effect of interleukin-8 (IL-8) on the EMT process in primary-cultured ameblastoma tumor cells (AM-P) and ameloblastoma immortalized tumor cells (AM-L) and its underlying mechanism.METHODS: IL-8 levels in ameloblastomas were detected by immunofluorescence staining and ELISA. AM-P cells and AM-L cells were stimulated with IL-8, and EMT transcription factors, total β-catenin and phosphorylated-β-catenin (p-β-catenin) levels were determined by Western blot analysis and immunofluorescence staining. β-catenin siRNA was used to knockdown β-catenin expression in AM-P cells and AM-L cells stimulated with IL-8.
    RESULTS: IL-8 was highly expressed in the solid ameloblastomas. IL-8 promoted the EMT process in ameloblastoma tumor cells in vitro, as evidenced by decreased E-cadherin and increased vimentin, twist and zeb1 levels. IL-8 also increased total β-catenin and p-β-catenin expression in ameloblastoma tumor cells, and β-catenin knockdown partially inhibited the EMT process in tumor cells, as evidenced by increased E-cadherin, and decreased vimentin and zeb1 levels.
    CONCLUSIONS: IL-8 could promote EMT in ameloblastoma tumor cells by activating β-catenin and its downstream transcription factor zeb1. This article is protected by copyright. All rights reserved.
    Keywords:  ameloblastoma; epithelial-mesenchymal transition; interleukin-8; zeb1; β-catenin
    DOI:  https://doi.org/10.1111/odi.13173
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