title: MACC1 is involved in the regulation of proliferation, colony formation, invasion ability, cell cycle distribution, apoptosis and tumorigenicity by altering Akt signaling pathway in human osteosarcoma.
abstract: There is mounting evidence that metastasis-associated in colon cancer-1 (MACC1) plays pivotal roles in development and progression of many tumors, particularly in osteosarcoma (OS). However, its precise roles and molecular mechanisms remain to be delineated in OS. In the current study, we found that the levels of MACC1 mRNA and protein in four OS cell lines (MG-63, HOS, SaOS-2 and U2OS) were significantly higher than that in hFOB1.19 osteoblast (P < 0.05). The vector pcDNA-MACC1 contributed to the increase of MACC1 level in MG-63 cells, whereas MACC1 siRNA evoked the decrease of MACC1 level in U2OS cells. In addition, MACC1 downregualtion caused the inhibition of cell proliferation in vitro, colony formation, invasion and tumor growth in vivo, arrested cell cycle in G0/G1 phase and induced cell apoptosis in U2OS cells, and reversed effects were observed in MG-63 cells by MACC1 upregulation. Most notably, MACC1 depletion markedly inactivated Akt signaling pathway in U2OS cells, conversely, MACC1 upregulation evidently activated Akt signaling pathway in MG-63 cells. Collectively, our data presented herein suggest that biological implications triggered by MACC1 may be tightly associated with the status of Akt signaling pathway in OS.
authors.affiliation: Department of Orthopaedics, Chinese PLA General Hospital & Chinese PLA Medical School, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Tian
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
authors.forename: Na
authors.initials: N
authors.lastname: Xue
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhu
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.forename: Xinjun
authors.initials: X
authors.lastname: Guo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C544162:MACC1 protein, human; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D051057:Proto-Oncogene Proteins c-akt