title: RASSF5 inhibits growth and invasion and induces apoptosis in osteosarcoma cells through activation of MST1/LATS1 signaling.
abstract: 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.
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Xu-Hui
authors.initials: XH
authors.lastname: Zhou
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Chao-Qun
authors.initials: CQ
authors.lastname: Yang
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Cheng-Lin
authors.initials: CL
authors.lastname: Zhang
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Yuan
authors.affiliation: Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Ce
authors.initials: C
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D055815:Young Adult; D000099317:Hippo Kinases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020780:Matrix Metalloproteinase 9; D020559:Monomeric GTP-Binding Proteins; D018809:Proliferating Cell Nuclear Antigen; D017346:Protein Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53; C454042:RASSF5 protein, human; C092745:LATS1 protein, human; C095566:STK4 protein, human; D000099317:Hippo Kinases; C579270:MMP9 protein, human