RASSF5 inhibits growth and invasion and induces apoptosis in osteosarcoma cells through activation of MST1/LATS1 signaling
| Autor: | Chenglin Zhang, Xuhui Zhou, Ce Wang, Hong-Bin Yuan, Yang Gao, Chao-Qun Yang |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
Cancer Research Cell Apoptosis Bone Neoplasms Protein Serine-Threonine Kinases Biology Real-Time Polymerase Chain Reaction medicine.disease_cause Young Adult Cell Line Tumor Proliferating Cell Nuclear Antigen medicine Humans Neoplasm Invasiveness Adaptor Proteins Signal Transducing Cell Proliferation Monomeric GTP-Binding Proteins Osteosarcoma Oncogene Cell growth Intracellular Signaling Peptides and Proteins General Medicine Cell cycle medicine.anatomical_structure Matrix Metalloproteinase 9 Oncology Cell culture Cancer research Female Tumor Suppressor Protein p53 Signal transduction Apoptosis Regulatory Proteins Carcinogenesis Signal Transduction |
| Zdroj: | Oncology Reports. 32:1505-1512 |
| ISSN: | 1791-2431 1021-335X |
| DOI: | 10.3892/or.2014.3387 |
| Popis: | Ras association (RalGDS/AF-6) domain family member RASSF5 has been implicated in a variety of key biological processes, including cell proliferation, cell cycle regulation and apoptosis. It is believed to play an important role in tumorigenesis as a tumor suppressor in a number of malignancies. Yet, little is known concerning the function and underlying mechanisms of RASSF5 in human osteosarcoma (OS). The expression of RASSF5 was examined by immunohistochemical assay using a tissue microarray in 45 cases of OS tissues. A gain-of-function approach was used to observe the effects of lentiviral vector-mediated overexpression of RASSF5 (Lv-RASSF5) on cell growth, invasion and apoptosis, respectively, as indicated by MTT, Transwell and flow cytometry assays, and the expression levels of mammalian sterile 20-like (MST1) kinase, large tumor suppressor 1 (LATS1), proliferating cell nuclear antigen (PCNA), matrix metallopeptidase-9 (MMP-9) and p53 were detected by real-time PCR and western blot assays in OS cells (MG-63 and U-2 OS). The results indicated that the expression of RASSF5 protein was significantly downregulated in OS tissues compared to that in adjacent non-cancerous tissues (ANCT) (40.0 vs. 73.3%, P=0.002), and had a negative correlation with distant metastasis of the tumor (P=0.01). Overexpression of RASSF5 markedly suppressed cell proliferation and invasion, and induced cell apoptosis in the OS cell lines with increased expression of MST1, LATS1 and p53 and decreased expression of PCNA and MMP-9. Taken together, our findings demonstrate that RASSF5 expression is negatively correlated with distant metastasis of OS, and RASSF5 may function as a tumor suppressor in OS cells through activation of the MST1/LATS1 pathway. |
| Databáze: | OpenAIRE |
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