TY - JOUR
T1 - Active Secretion of Dimerized S100A11 Induced by the Peroxisome in Mesothelioma Cells
AU - Saho, Satomi
AU - Satoh, Hiroki
AU - Kondo, Eisaku
AU - Inoue, Yusuke
AU - Yamauchi, Akira
AU - Murata, Hitoshi
AU - Kinoshita, Rie
AU - Yamamoto, Ken ichi
AU - Futami, Junichiro
AU - Putranto, Endy Widya
AU - Ruma, I. Made Winarsa
AU - Sumardika, I. Wayan
AU - Youyi, Chen
AU - Suzawa, Ken
AU - Yamamoto, Hiromasa
AU - Sou, Junichi
AU - Tomida, Shuta
AU - Sakaguchi, Yoshihiko
AU - Saito, Ken
AU - iioka, Hidekazu
AU - Huh, Nam ho
AU - Toyooka, Shinichi
AU - Sakaguchi, Masakiyo
N1 - Funding Information:
This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Grant–in-Aid for Scientific Research (B), No. 26290039; Grant–in-Aid for Challenging Exploratory Research, No. 15 K14382) (M. Sakaguchi), from the Takeda Science Foundation (M. Sakaguchi), from the Princess Takamatsu Cancer Research Fund (14–24613; M. Sakaguchi), and from the Kobayashi Foundation for Cancer Research (M. Sakaguchi).
Publisher Copyright:
© 2016, Springer Science+Business Media Dordrecht.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
KW - Lysosome
KW - Mesothelioma
KW - Metastasis
KW - Peroxisome
KW - S100A11
KW - Tumor microenvironment
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U2 - 10.1007/s12307-016-0185-2
DO - 10.1007/s12307-016-0185-2
M3 - Article
C2 - 27334300
AN - SCOPUS:84975523212
VL - 9
SP - 93
EP - 105
JO - Cancer Microenvironment
JF - Cancer Microenvironment
SN - 1875-2292
IS - 2-3
ER -