title: TWIST interacts with β-catenin signaling on osteosarcoma cell survival against cisplatin.
abstract: Both TWIST and Wnt/β-catenin signaling reportedly play important roles in osteosarcoma development. In the present study, we explored the regulatory effect of TWIST on β-catenin in osteosarcoma cells and assessed how the functional interaction between TWIST and β-catenin would impact osteosarcoma cell survival against chemotherapy agent cisplatin. Overexpression and knockdown of TWIST were respectively performed in Saos-2 and MG-63 osteosarcoma cells. Overexpression of TWIST in Saos-2 cells significantly decreased the soluble β-catenin level, phosphorylation of glycogen synthase kinase-3β (GSK-3β) at serine 9, the mRNA level of β-catenin signaling target genes, and cell survival against cisplatin, which was strengthened by knocking down β-catenin. Knockdown of TWIST in MG-63 cells significantly increased the soluble β-catenin level, phosphorylation of GSK-3β at serine 9, the mRNA level of β-catenin signaling target genes, and cell survival against cisplatin, which was reversed by knocking down β-catenin or phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. In conclusion, we demonstrate that TWIST decreases osteosarcoma cell survival against cisplatin by decreasing the soluble β-catenin level through a PI3K-dependent manner. This study provides the first evidence of a functional link between TWIST and β-catenin signaling in osteosarcoma cells, which adds fresh insights into the molecular mechanism of osteosarcoma development.
authors.affiliation: Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Spine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jianhuang
authors.initials: J
authors.lastname: Wu
authors.forename: Qiande
authors.initials: Q
authors.lastname: Liao
authors.forename: Hongbo
authors.initials: H
authors.lastname: He
authors.forename: Da
authors.initials: D
authors.lastname: Zhong
authors.forename: Ke
authors.initials: K
authors.lastname: Yin
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051879:Twist-Related Protein 1; D051176:beta Catenin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin
keywords: TWIST; cell survival; cisplatin; osteosarcoma; β-catenin