title: CD151 knockdown inhibits osteosarcoma metastasis through the GSK-3β/β-catenin/MMP9 pathway.
abstract: Osteosarcoma (OS) is a primary bone malignancy with a high early metastatic propensity. It is crucial to find specific protein targets to develop therapeutic strategies against this lethal disease. Tetraspanin CD151 is involved in facilitating tumor metastasis. However, the role and molecular mechanism of CD151 in promoting OS metastasis remain enigmatic. In the present study, we used small interfering RNA (siRNA) to inhibit CD151 expression in highly metastatic OS cells and the results demonstrated that CD151 knockdown inhibited their migration, invasion and metastasis. We further investigated the molecular mechanism of CD151 by inhibiting genes known to be involved in metastasis in OS cells and found that CD151 modulated matrix metalloproteinase 9 (MMP9) expression through the glycogen synthase kinase 3 (GSK-3β)/β-catenin signaling pathway. We conclude that CD151 knockdown inhibits the expression of MMP9 through the GSK-3β/β‑catenin pathway and also inhibits OS migration and invasion in vitro and metastasis in vivo in highly metastatic OS. This suggests that CD151 may be a useful antimetastatic target for OS.
authors.affiliation: Department of Orthopaedics, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Laboratory Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China.
authors.forename: Haifei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Orthopaedics, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China.
authors.forename: Chengbin
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Laboratory Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China.
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Orthopaedics, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D055785:Gene Knockdown Techniques; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation; D034741:RNA, Small Interfering; D060185:Tetraspanin 24 / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; D060185:Tetraspanin 24; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D020780:Matrix Metalloproteinase 9