title: Eukaryotic translation elongation factor 1A induces anoikis by triggering cell detachment.
abstract: Anoikis, apoptosis because of loss of cell anchorage, is crucial for tissue homeostasis. Fibronectin not only provides a scaffold for cell anchorage but also harbors a cryptic antiadhesive site capable of inducing β1-integrin inactivation. In this study, this cryptic antiadhesive site is implicated in spontaneous induction of anoikis. Nontransformed fibroblasts (NIH3T3) adhering to a fibronectin substratum underwent anoikis during serum starvation culture. This anoikis was caused by proteolytic exposure of the cryptic antiadhesive site in fibronectin by matrix metalloproteinase. Eukaryotic elongation factor 1A (eEF1A) was identified as a membrane receptor for the exposed antiadhesive site. Serum starvation raised the membrane residence of eEF1A, and siRNA-based disruption of this increase rendered cells anoikis-resistant. By contrast, cells became more susceptible to anoikis in parallel with increased membrane residence of eEF1A by enforced expression. These results demonstrate that eEF1A acts as a membrane receptor for the cryptic antiadhesive site of fibronectin, which contributes to cell regulation, including anoikis, through negative regulation of cell anchorage.
authors.affiliation: Department of Molecular Pathophysiology, Tokyo University of Science, Chiba 278-8510, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Itagaki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Naito
authors.forename: Ryota
authors.initials: R
authors.lastname: Iwakiri
authors.forename: Makoto
authors.initials: M
authors.lastname: Haga
authors.forename: Shougo
authors.initials: S
authors.lastname: Miura
authors.forename: Yohei
authors.initials: Y
authors.lastname: Saito
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Owaki
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Kamiya
authors.forename: Takuya
authors.initials: T
authors.lastname: Iyoda
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yajima
authors.forename: Shintaro
authors.initials: S
authors.lastname: Iwashita
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Ejiri
authors.forename: Fumio
authors.initials: F
authors.lastname: Fukai
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023102:Anoikis / Q000187:drug effects / Q000502:physiology*; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D015977:Eukaryotic Initiation Factor-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D020014:K562 Cells; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference
chemical_list: D016895:Culture Media, Serum-Free; D015977:Eukaryotic Initiation Factor-1; D005353:Fibronectins; D020648:Peptide Elongation Factor 1; C026022:eukaryotic peptide initiation factor-1A