title: The O‑glycosylation mutant osteopontin alters lung cancer cell growth and migration in vitro and in vivo.
abstract: Osteopontin (OPN) is an acidic, glycosylated and phosphorylated protein that plays an essential role in determining the aggressiveness and oncogenic potential of several types of cancer, including lung cancer. The OPN function is highly dependent on post-translational modification (PTM) and regulation of the processes that involve OPN can be mediated through glycosylation. However, the connection between OPN function and its O-glycosylation in lung cancer cells has yet to be investigated. In the present study, this issue was addressed by studying the effects of wild-type (WT) OPN and a triple mutant (TM) of OPN, which was mutated at three O-glycosylation sites in lung cancer cells. It was shown that OPN WT rather than OPN TM induced the OPN‑mediated signaling pathway. The OPN WT expression enhanced cap-dependent protein translation, NF-κB activity and glucose uptake, whereas a reduction was observed in cells treated with OPN TM. The results clearly demonstrated that unlike OPN WT, OPN TM did not increase lung cancer cell growth and migration both in vitro and in a xenograft mouse model. Thus, results of the present study suggested that targeting OPN by introducing OPN TM may be a good strategy for treating lung cancer.
authors.affiliation: Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151‑742, Japan.
authors.forename: Arash
authors.initials: A
authors.lastname: Minai-Tehrani
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Chang
authors.forename: Seung Bum
authors.initials: SB
authors.lastname: Park
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D006031:Glycosylation; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D009154:Mutation; D053495:Osteopontin / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D053495:Osteopontin