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?ig-h3 promotes human osteosarcoma cells metastasis by interacting with integrin ?2?1 and activating PI3K signaling pathway.

ABSTRACT: Osteosarcoma, the most common primary bone tumor in children and young adolescents, is characterized by local invasion and distant metastasis. But the detailed mechanisms of osteosarcoma metastasis are not well known. In the present study, we found that ?ig-h3 promotes metastatic potential of human osteosarcoma cells in vitro and in vivo. Furthermore, ?ig-h3 co-localized with integrin ?2?1 in osteosarcoma cells. But ?ig-h3 did not change integrin ?2?1 expression in Saos-2 cells. Interaction of ?ig-h3 with integrin ?2?1 mediates metastasis of human osteosarcoma cells. The second FAS1 domain of ?ig-h3 but not the first FAS1 domain, the third FAS1 domain or the fourth FAS1 domain mediates human osteosarcoma cells metastasis, which is the ?2?1 integrin-interacting domain. We further demonstrated that PI3K/AKT signaling pathway is involved in ?ig-h3-induced human osteosarcoma cells metastasis process. Together, these results reveal ?ig-h3 enhances the metastasis potentials of human osteosarcoma cells via integrin ?2?1-mediated PI3K/AKT signal pathways. The discovery of ?ig-h3-mediated pathway helps us to understand the mechanism of human osteosarcoma metastasis and provides evidence for the possibility that ?ig-h3 can be a potential therapeutic target for osteosarcoma treatment.

SUBMITTER: Guo YS

PROVIDER: S-EPMC3942417 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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βig-h3 promotes human osteosarcoma cells metastasis by interacting with integrin α2β1 and activating PI3K signaling pathway.

Guo Yun-Shan YS Zhao Rui R Ma Jie J Cui Wei W Sun Zhen Z Gao Bo B He Shu S Han Yue-Hu YH Fan Jing J Yang Liu L Tang Juan J Luo Zhuo-Jing ZJ

PloS one 20140304 3

Osteosarcoma, the most common primary bone tumor in children and young adolescents, is characterized by local invasion and distant metastasis. But the detailed mechanisms of osteosarcoma metastasis are not well known. In the present study, we found that βig-h3 promotes metastatic potential of human osteosarcoma cells in vitro and in vivo. Furthermore, βig-h3 co-localized with integrin α2β1 in osteosarcoma cells. But βig-h3 did not change integrin α2β1 expression in Saos-2 cells. Interaction of β ...[more]

PMID: 24595049

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Project description:Hepatocellular carcinoma (HCC) is a malignant tumor with a high metastatic rate. Recent studies have shown that the mitosis‑associated spindle‑assembly checkpoint regulatory protein spindle pole body component 25 homolog (SPC25) promotes HCC progression, although the underlying mechanism has yet to be fully elucidated. The aim of the present study was to investigate the mechanism through which SPC25 may promote HCC progression in greater detail. First, the expression of SPC25 was analyzed in publicly available databases to explore the association between SPC25 and HCC metastasis. Western blotting was subsequently performed to examine the level of SPC25 expression in different HCC cell lines. SPC25 was then silenced in HCCLM3 and Huh7 cells, and the effects of SPC25 silencing were investigated using cell proliferation, wound‑healing, Transwell migration assays and an in vivo mouse model. Finally, the mechanism of SPC25 action with respect to the promotion of HCC metastasis was explored using microarray analysis and rescue experiments. The results obtained demonstrated that SPC25 is highly expressed in HCC, and this high level of expression is associated with poor prognosis and metastasis. Moreover, SPC25 silencing led to a marked inhibition of the invasion and migration of HCC cells both in vitro and in vivo. The gene‑expression profiling and mechanistic experiments suggest that SPC25 preferentially influences the expression of genes associated with extracellular matrix (ECM)‑integrin interactions, including integrin subunit β4 (ITGB4), an upstream element of the integrin pathway. ITGB4 upregulation partly reversed the decline in cell invasion and migration capacities that resulted from SPC25 silencing. Furthermore, deleting both SPC25 and ITGB4 caused a decrease in the phosphorylation of focal adhesion kinase (FAK), phosphoinositide 3‑kinase (PI3K) and AKT, which are downstream elements of the integrin pathway. Taken together, the results of the present study demonstrated the important role of SPC25 as a prognostic indicator and as a promoter of metastasis in HCC, and the underlying mechanism of its action has been partially elucidated, suggesting that SPC25 could be used as a biomarker and as a target for therapeutic intervention in the treatment of HCC.

Dataset Information

?ig-h3 promotes human osteosarcoma cells metastasis by interacting with integrin ?2?1 and activating PI3K signaling pathway.

Publications

βig-h3 promotes human osteosarcoma cells metastasis by interacting with integrin α2β1 and activating PI3K signaling pathway.

Similar Datasets

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