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

Yamada, Tamaki  ,  Tsuda, Masumi  ,  Wagatsuma, Takanori  ,  Fujioka, Yoichiro  ,  Fujioka, Mari  ,  Satoh, Aya O.  ,  Horiuchi, Kosui  ,  Nishide, Shinya  ,  Nanbo, Asuka  ,  Totsuka, Yasunori  ,  Haga, Hisashi  ,  Tanaka, Shinya  ,  Shindoh, Masanobu  ,  Ohba, Yusuke

6p.23545 , 2016-03-24 , Nature Publishing Group
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.

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