ID | 65209 |
フルテキストURL | |
著者 |
Komalasari, Ni Luh Gede Yoni
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
Chen, Youyi
Department of General Surgery & Bio-Bank of General Surgery, TheFourth Affiliated Hospital of Harbin Medical University
Sakaguchi, Yoshihiko
Department of Microbiology, Kitasato University School of Medicine
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
Yamamoto, Ken-Ich
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
Kaken ID
publons
researchmap
Ruma, I Made Winarsa
Faculty of Medicine, Udayana University
Sumardika, I Wayan
Faculty of Medicine, Udayana University
Zhou, Jin
Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology
Yamauchi, Akira
Department of Biochemistry, Kawasaki Medical School
Kuribayashi, Futoshi
Department of Biochemistry, Kawasaki Medical School
Inoue, Yusuke
Faculty of Science and Technology, Division of Molecular Science, Gunma University
Toyooka, Shinichi
Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
Kaken ID
publons
researchmap
Sakaguchi, Masakiyo
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
Kaken ID
publons
researchmap
|
抄録 | Background: LOX family members are reported to play pivotal roles in cancer. Unlike their enzymatic activities in collagen cross-linking, their precise cancer functions are unclear. We revealed that LOXL4 is highly upregulated in breast cancer cells, and we thus sought to define an unidentified role of LOXL4 in breast cancer.
Methods: We established the MDA-MB-231 sublines MDA-MB-231-LOXL4 mutCA and -LOXL4 KO, which stably overexpress mutant LOXL4 that loses its catalytic activity and genetically ablates the intrinsic LOXL4 gene, respectively. In vitro and in vivo evaluations of these cells’ activities of cancer outgrowth were conducted by cell-based assays in cultures and an orthotopic xenograft model, respectively. The new target (s) of LOXL4 were explored by the MS/MS analytic approach. Results: Our in vitro results revealed that both the overexpression of mutCA and the KO of LOXL4 in cells resulted in a marked reduction of cell growth and invasion. Interestingly, the lowered cellular activities observed in the engineered cells were also reflected in the mouse model. We identified a novel binding partner of LOXL4, i.e., annexin A2. LOXL4 catalyzes cell surface annexin A2 to achieve a cross-linked multimerization of annexin A2, which in turn prevents the internalization of integrin β-1, resulting in the locking of integrin β-1 on the cell surface. These events enhance the promotion of cancer cell outgrowth. Conclusions: LOXL4 has a new role in breast cancer progression that occurs via an interaction with annexin A2 and integrin β-1 on the cell surface. |
キーワード | breast cancer
lysyl oxidase
annexin A2
integrin
cancer microenvironment
|
発行日 | 2023-04-04
|
出版物タイトル |
Frontiers in Oncology
|
巻 | 13巻
|
出版者 | Frontiers Media
|
開始ページ | 1142907
|
ISSN | 2234-943X
|
資料タイプ |
学術雑誌論文
|
言語 |
英語
|
OAI-PMH Set |
岡山大学
|
著作権者 | © 2023 Komalasari, Tomonobu, Kinoshita, Chen, Sakaguchi, Gohara, Jiang, Yamamoto, Murata, Ruma, Sumardika, Zhou, Yamauchi, Kuribayashi, Inoue, Toyooka and Sakaguchi.
|
論文のバージョン | publisher
|
PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.3389/fonc.2023.1142907
|
ライセンス | https://creativecommons.org/licenses/by/4.0/
|
Citation | Komalasari NLGY, Tomonobu N, Kinoshita R, Chen Y, Sakaguchi Y, Gohara Y, Jiang F, Yamamoto K-i, Murata H, Ruma IMW, Sumardika IW, Zhou J, Yamauchi A, Kuribayashi F, Inoue Y, Toyooka S and Sakaguchi M (2023) Lysyl oxidase-like 4 exerts an atypical role in breast cancer progression that is dependent on the enzymatic activity that targets the cell-surface annexin A2. Front. Oncol. 13:1142907. doi: 10.3389/fonc.2023.1142907
|
助成機関名 |
Japan Society for the Promotion of Science
|
助成番号 | 20H03516
|