title: Silencing of galectin-3 represses osteosarcoma cell migration and invasion through inhibition of FAK/Src/Lyn activation and β-catenin expression and increases susceptibility to chemotherapeutic agents.
abstract: Galectin-3 is involved in tumor cell proliferation, adhesion, angiogenesis and metastasis. Galectin-3 promotes β-catenin/Wnt signaling, and β-catenin-related oncogenesis has been frequently reported in osteosarcoma. However, the correlation between galectin-3 and β‑catenin signaling in osteosarcoma is poorly defined. We hypothesized that galectin-3 may control the migration and invasion of cancer cells and that silencing of galectin-3 would therefore, suppress motility in osteosarcoma cells. In the present study, we show that galectin-3 silencing in cultured human osteosarcoma cells had decreased cell migration and invasion capabilities; reduced the expression and activation of FAK, Src, Lyn, PI3K/Akt, ERK1/2 and β-catenin, which are key mediators of invasion; inhibited the expression and secretion of VEGF, MCP-1, IL-8, IL-6, MMP2/9 and phospho-Stat3; and potentiated sensitivity to cisplatin. Our results suggest that galectin-3 may be a feasible therapeutic target for osteosarcoma.
authors.affiliation: Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Ga Bin
authors.initials: GB
authors.lastname: Park
authors.affiliation: Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Dae-Jin
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Yeong-Seok
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Department of Orthopedic Surgery, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.
authors.forename: Chang Wan
authors.initials: CW
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine, Busan 614-735, Republic of Korea.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Hur
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D037502:Galectin 3 / Q000037:antagonists & inhibitors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C495270:CTNNB1 protein, human; D037502:Galectin 3; D051176:beta Catenin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases