FAM83H is involved in stabilization of β-catenin and progression of osteosarcomas

Abstract

Background FAM83H was initially identified as a protein essential for dental enamel formation. Recent reports have shown that FAM83H is also involved in the progression of human cancers in conjunction with tumor-associated molecules, such as MYC and β-catenin. However, the role of FAM83H in sarcoma has not yet been investigated. Methods The expression and roles of FAM83H and β-catenin were evaluated in human osteosarcomas from 34 patients and osteosarcoma cells. Results The expression of nuclear FAM83H, cytoplasmic FAM83H, and β-catenin were significantly associated with each other and significantly associated with shorter survival of osteosarcoma patients by univariate analysis. In multivariate analysis, cytoplasmic expression of FAM83H was an independent indicator of shorter survival of osteosarcoma patients (overall survival; P < 0.001, relapse-free survival; P < 0.001). In U2OS, MG63, and KHOS/NP osteosarcoma cells, the knock-down of FAM83H decreased proliferation and invasion activity and overexpression of FAM83H increased proliferation and invasion activity. In KHOS/NP cells, knock-down of FAM83H significantly inhibited, and overexpression of FAM83H significantly increased in vivo growth of cells. In addition, the knock-down of FAM83H decreased protein expression of β-catenin, active β-catenin, cyclin D1, vimentin, and snail. Overexpression of FAM83H increased protein expression of β-catenin, active β-catenin, cyclin D1, vimentin, and snail. However, the expression of β-catenin mRNA was not significantly altered with knock-down or overexpression of FAM83H. In addition, FAM83H and β-catenin shown to directly interact via immunoprecipitation and nuclear and cytoplasmic localization of β-catenin was decreased with knock-down of FAM83H. Moreover, the ubiquitination and proteasomal degradation of β-catenin was increased with knock-down of FAM83H. Conclusions This study suggests that FAM83H is involved in the progression of osteosarcomas via a mechanism involving the stabilization of β-catenin and the promotion of proliferation and invasiveness of osteosarcomas.

Circ_0001658 promotes the proliferation and metastasis of osteosarcoma cells via regulating miR‐382‐5p/YB‐1 axis

“…Osteosarcoma (OS) is a common primary malignant bone tumour among children and adolescents, frequently diagnosed in the distal femur, the proximal tibia, and the proximal humerus . Though multiple treatments offer symptomatic relief and modest improvement in survival for OS patients, the long‐term disease‐free survival rate of patients remains unfavourable, only 60% to 75% . To make matters worse, the 5‐year survival rate was only 27% to 55% in patients with local relapsing and distant metastasis treated by the available therapy clinically .…”

Expression of FAM83H and ZNF16 are associated with shorter survival of patients with gallbladder carcinoma

“…Therefore, using established targeted therapeutic molecules which block cellular proliferation and invasiveness might be beneficial in the treatment of gallbladder carcinoma patients with tumors with high expression of FAM83H/ZNF16. Especially, MYC and the Wnt/β-catenin pathway might be a potential therapeutic targets of gallbladder carcinomas with high expression of FAM83H/ZNF16 because MYC is a transcriptional regulator of FAM83H and FAM83H stabilizes βcatenin [5,6,28,29]. In addition, FAM83H is involved in the invasiveness of cancer cells through the EMT pathway in hepatocellular carcinoma and osteosarcoma [5,6].…”

“…However, recent reports have shown various roles of FAM83H in both normal cells and cancer cells. In addition to the role of FAM83H in enamel formation in teeth, it is important in maintaining the intracellular actin filament framework and is involved in cancer progression [3][4][5][6]. Expression of FAM83H in cancer cells is elevated compared with normal cells, which suggests FAM83H plays a role in tumorigenesis [7].…”

“…Disruption of the actin filament network by deregulated FAM83H expression is thought to induce epithelial-to-mesenchymal transition (EMT) [3]. FAM83H-mediated stimulation of EMT accelerates cancer progression [5,6]. Moreover, FAM83H stimulates the proliferation of cancer cells by inducing cell cycle progression in conjunction with MYC and canonical Wnt pathways [5,6].…”

“…FAM83H-mediated stimulation of EMT accelerates cancer progression [5,6]. Moreover, FAM83H stimulates the proliferation of cancer cells by inducing cell cycle progression in conjunction with MYC and canonical Wnt pathways [5,6]. The oncogene MYC transcriptionally stimulates FAM83H expression, and consequently, FAM83H stabilizes β-catenin to activate the canonical Wnt pathway [5].…”