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Receptor activator of NF-κB ligand induces cell adhesion and integrin α2 expression via NF-κB in head and neck cancers

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Title: Receptor activator of NF-κB ligand induces cell adhesion and integrin α2 expression via NF-κB in head and neck cancers
Authors: Yamada, Tamaki Browse this author →KAKEN DB
Tsuda, Masumi Browse this author →KAKEN DB
Wagatsuma, Takanori Browse this author
Fujioka, Yoichiro Browse this author
Fujioka, Mari Browse this author
Satoh, Aya O. Browse this author
Horiuchi, Kosui Browse this author
Nishide, Shinya Browse this author →KAKEN DB
Nanbo, Asuka Browse this author →KAKEN DB
Totsuka, Yasunori Browse this author →KAKEN DB
Haga, Hisashi Browse this author →KAKEN DB
Tanaka, Shinya Browse this author →KAKEN DB
Shindoh, Masanobu Browse this author →KAKEN DB
Ohba, Yusuke Browse this author →KAKEN DB
Issue Date: 24-Mar-2016
Publisher: Nature Publishing Group
Journal Title: Scientific reports
Volume: 6
Start Page: 23545
Publisher DOI: 10.1038/srep23545
Abstract: Cellular interactions with the extracellular matrix play critical roles in tumor progression. We previously reported that receptor activator of NF-κB ligand (RANKL) specifically facilitates head and neck squamous cell carcinoma (HNSCC) progression in vivo. Here, we report a novel role for RANKL in the regulation of cell adhesion. Among the major type I collagen receptors, integrin α2 was significantly upregulated in RANKL-expressing cells, and its knockdown suppressed cell adhesion. The mRNA abundance of integrin α2 positively correlated with that of RANKL in human HNSCC tissues. We also revealed that RANK-NF-κB signaling mediated integrin α2 expression in an autocrine/paracrine manner. Interestingly, the amount of active integrin β1 on the cell surface was increased in RANKL-expressing cells through the upregulation of integrin α2 and endocytosis. Moreover, the RANK-integrin α2 pathway contributed to RANKL-dependent enhanced survival in a collagen gel and inhibited apoptosis in a xenograft model, demonstrating an important role for RANKL-mediated cell adhesion in three-dimensional environments.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 大場 雄介

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