ID | 65043 |
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Hirabayashi, Daisuke
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yamamoto, Ken-ichi
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Maruyama, Akihiro
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Tomonobu, Nahoko
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kinoshita, Rie
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Chen, Youyi
Department of General Surgery & Bio-Bank of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University
Komalasari, Ni Luh Gede Yoni
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Murata, Hitoshi
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Gohara, Yuma
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Jiang, Fan
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Zhou, Jin
Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of the Dalian University of Technology
Ruma, I. Made Winarsa
Faculty of Medicine, Udayana University
Sumardika, I. Wayan
Faculty of Medicine, Udayana University
Yamauchi, Akira
Department of Biochemistry, Kawasaki Medical School
Kuribayashi, Futoshi
Department of Biochemistry, Kawasaki Medical School
Toyooka, Shinichi
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Inoue, Yusuke
Faculty of Science and Technology, Division of Molecular Science, Gunma University
Sakaguchi, Masakiyo
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Abstract | Background: EMT has been proposed to be a crucial early event in cancer metastasis. EMT is rigidly regulated by the action of several EMT-core transcription factors, particularly ZEB1. We previously revealed an unusual role of ZEB1 in the S100A8/A9-mediated metastasis in breast cancer cells that expressed ZEB1 at a significant level and showed that the ZEB1 was activated on the MCAM-downstream pathway upon S100A8/A9 binding. ZEB1 is well known to require Zn2+ for its activation based on the presence of several Zn-finger motifs in the transcription factor. However, how Zn2+-binding works on the pleiotropic role of ZEB1 through cancer progression has not been fully elucidated.
Methods: We established the engineered cells, MDA-MB-231 MutZEB1 (MDA-MutZEB1), that stably express MutZEB1 (Delta Zn). The cells were then evaluated in vitro for their invasion activities. Finally, an RNA-Seq analysis was performed to compare the gene alteration profiles of the established cells comprehensively. Results: MDA-MutZEB1 showed a significant loss of the EMT, ultimately stalling the invasion. Inclusive analysis of the transcription changes after the expression of MutZEB1 (Delta Zn) in MDA-MB-231 cells revealed the significant downregulation of LOX family genes, which are known to play a critical role in cancer metastasis. We found that LOXL1 and LOXL4 remarkably enhanced cancer invasiveness among the LOX family genes with altered expression. Conclusions: These findings indicate that ZEB1 potentiates Zn2+-mediated transcription of plural EMT-relevant factors, including LOXL1 and LOXL4, whose upregulation plays a critical role in the invasive dissemination of breast cancer cells. |
Keywords | epithelial-to-mesenchymal transition
triple-negative breast cancer
zinc
ZEB1
metastasis
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Published Date | 2023-02-23
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Publication Title |
Frontiers in Oncology
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Volume | volume13
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Publisher | Frontiers Media
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Start Page | 1142886
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ISSN | 2234-943X
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © 2023 Hirabayashi, Yamamoto, Maruyama, Tomonobu, Kinoshita, Chen, Komalasari, Murata, Gohara, Jiang, Zhou, Ruma, Sumardika, Yamauchi, Kuribayashi, Toyooka, Inoue and Sakaguchi.
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File Version | publisher
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Related Url | isVersionOf https://doi.org/10.3389/fonc.2023.1142886
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License | https://creativecommons.org/licenses/by/4.0/
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Funder Name |
Japan Society for the Promotion of Science
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助成番号 | 20H03516
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