title: Active Secretion of Dimerized S100A11 Induced by the Peroxisome in Mesothelioma Cells.
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.
authors.affiliation: Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Saho
authors.affiliation: Department of Thoracic, Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Satoh
authors.affiliation: Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, 757, Ichiban-cho, Asahimachi-dori, Chuo-ku, Niigata-shi, Niigata, 951-8510, Japan.
authors.forename: Eisaku
authors.initials: E
authors.lastname: Kondo
authors.affiliation: Faculty of Science and Technology, Division of Molecular Science, Gunma University, 1-5-1 Tenjin-cho, Kiryu-shi, Gunma, 376-8515, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Biochemistry, Kawasaki Medical School, 577 Matsushima, Kurashiki-shi, Okayama, 701-0192, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamauchi
authors.affiliation: Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Murata
authors.affiliation: Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Kinoshita
authors.affiliation: Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Yamamoto
authors.affiliation: Department of Medical and Bioengineering Science, Okayama University Graduate School of Natural Science and Technology, 3-1-1, Tsushima-Naka, Kita-ku, Okayama, 700-8530, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Futami
authors.affiliation: Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan.|Faculty of Medicine, Gajah Mada University, Yogyakarta, 55281, Indonesia.
authors.forename: Endy Widya
authors.initials: EW
authors.lastname: Putranto
authors.affiliation: Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan.|Faculty of Medicine, Udayana University, Denpasar, 80232, Bali, Indonesia.
authors.forename: I Made Winarsa
authors.initials: IM
authors.lastname: Ruma
authors.affiliation: Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan.|Faculty of Medicine, Udayana University, Denpasar, 80232, Bali, Indonesia.
authors.forename: I Wayan
authors.initials: IW
authors.lastname: Sumardika
authors.affiliation: Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan.
authors.forename: Chen
authors.initials: C
authors.lastname: Youyi
authors.affiliation: Department of Thoracic, Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Suzawa
authors.affiliation: Department of Thoracic, Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Thoracic, Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Soh
authors.affiliation: Department of Biobank, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
authors.forename: Shuta
authors.initials: S
authors.lastname: Tomida
authors.affiliation: Department of Microbiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Sakaguchi
authors.affiliation: Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, 757, Ichiban-cho, Asahimachi-dori, Chuo-ku, Niigata-shi, Niigata, 951-8510, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Saito
authors.affiliation: Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, 757, Ichiban-cho, Asahimachi-dori, Chuo-ku, Niigata-shi, Niigata, 951-8510, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Iioka
authors.affiliation: Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan.
authors.forename: Nam-Ho
authors.initials: NH
authors.lastname: Huh
authors.affiliation: Department of Thoracic, Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.|Department of Clinical Genomic Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.affiliation: Department of Cell Biology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan. masa-s@md.okayama-u.ac.jp.
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sakaguchi
keywords: Lysosome; Mesothelioma; Metastasis; Peroxisome; S100A11; Tumor microenvironment