Receptor activator of NF-?B ligand induces cell adhesion and integrin ?2 expression via NF-?B in head and neck cancers.

ABSTRACT: Cellular interactions with the extracellular matrix play critical roles in tumor progression. We previously reported that receptor activator of NF-?B 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 ?2 was significantly upregulated in RANKL-expressing cells, and its knockdown suppressed cell adhesion. The mRNA abundance of integrin ?2 positively correlated with that of RANKL in human HNSCC tissues. We also revealed that RANK-NF-?B signaling mediated integrin ?2 expression in an autocrine/paracrine manner. Interestingly, the amount of active integrin ?1 on the cell surface was increased in RANKL-expressing cells through the upregulation of integrin ?2 and endocytosis. Moreover, the RANK-integrin ?2 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.

SUBMITTER: Yamada T 

PROVIDER: S-EPMC4806381 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature