Active Secretion of Dimerized S100A11 Induced by the Peroxisome in Mesothelioma Cells

Satomi Saho, Hiroki Satoh, Eisaku Kondo, Yusuke Inoue, Akira Yamauchi, Hitoshi Murata, Rie Kinoshita, Ken ichi Yamamoto, Junichiro Futami, Endy Widya Putranto, I. Made Winarsa Ruma, I. Wayan Sumardika, Chen Youyi, Ken Suzawa, Hiromasa Yamamoto, Junichi Sou, Shuta Tomida, Yoshihiko Sakaguchi, Ken Saito, Hidekazu IiokaNam ho Huh, Shinichi Toyooka, Masakiyo Sakaguchi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

S100A11, a small Ca2+ binding protein, acts extracellularly as a mediator of cancer progression. That raises the question of how a protein that lacks the classical secretory signal is able to be secreted outside cells without being damaged. Some insights into this question have been obtained, and there has been accumulating evidence indicating a pivotal role of a non-classical vesicle-mediated pathway using lysosomes or peroxisomes for the protein secretion. To obtain a more precise insight into the secretory mechanism of S100A11, we first screened representative cancer cells exhibiting significantly active secretion of S100A11. From the results of profiling, we turned our attention to aggressive cancer mesothelioma cells. In mesothelioma cells, we found that abundant dimeric S100A11 was produced selectively in the peroxisome after transportation of monomeric S100A11 through an interaction with PEX14, a peroxisome membrane protein, resulting in peroxisomal secretion of dimerized S100A11. In an extracellular environment in vitro, dimerized S100A11 promoted mesothelial cell invasion indirectly with the help of fibroblast cells. Overall, the results indicate that the peroxisome functions as an essential vesicle for the production of dimerized S100A11 and the subsequent secretion of the protein from mesothelioma cells and that peroxisome-mediated secretion of dimerized S100A11 might play a critical role in mesothelioma progression in a tumor microenvironment.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalCancer Microenvironment
DOIs
Publication statusPublished - Jun 22 2016

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Keywords

  • Lysosome
  • Mesothelioma
  • Metastasis
  • Peroxisome
  • S100A11
  • Tumor microenvironment

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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