title: Receptor activator of NF-κB ligand induces cell adhesion and integrin α2 expression via NF-κB 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-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.
authors.affiliation: Department of Cell Physiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.|Division of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.|Laboratory of Oral and Maxillofacial Surgery, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Tsuda
authors.affiliation: Department of Cell Physiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Wagatsuma
authors.affiliation: Department of Cell Physiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Fujioka
authors.affiliation: Department of Cell Physiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Fujioka
authors.affiliation: Department of Cell Physiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Aya O
authors.initials: AO
authors.lastname: Satoh
authors.affiliation: Department of Cell Physiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Kosui
authors.initials: K
authors.lastname: Horiuchi
authors.affiliation: Department of Cell Physiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Nishide
authors.affiliation: Department of Cell Physiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Nanbo
authors.affiliation: Laboratory of Oral and Maxillofacial Surgery, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Totsuka
authors.affiliation: Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, Sapporo 060-0810, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Haga
authors.affiliation: Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Division of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Shindoh
authors.affiliation: Department of Cell Physiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohba
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009368:Neoplasm Transplantation; D053245:RANK Ligand / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D039421:Integrin alpha2; D016328:NF-kappa B; D053245:RANK Ligand; C505688:TNFSF11 protein, human