1. Receptor activator of NF-κB ligand induces cell adhesion and integrin α2 expression via NF-κB in head and neck cancers
- Author
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Masumi Tsuda, Hisashi Haga, Aya O. Satoh, Yoichiro Fujioka, Tamaki Yamada, Yusuke Ohba, Takanori Wagatsuma, Masanobu Shindoh, Mari Fujioka, Asuka Nanbo, Shinya Tanaka, Shin-ya Nishide, Kosui Horiuchi, and Yasunori Totsuka
- Subjects
0301 basic medicine ,musculoskeletal diseases ,Cell Survival ,Integrin ,Integrin alpha2 ,Biology ,Article ,03 medical and health sciences ,Paracrine signalling ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Cell Adhesion ,Animals ,Humans ,Cell adhesion ,Autocrine signalling ,Multidisciplinary ,RANK Ligand ,NF-kappa B ,NF-κB ,medicine.disease ,Head and neck squamous-cell carcinoma ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,chemistry ,RANKL ,Head and Neck Neoplasms ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,biology.protein ,Carcinoma, Squamous Cell ,Signal transduction ,Neoplasm Transplantation ,Signal Transduction - 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.
- Published
- 2016
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