Downregulation of HOPX controls metastatic behavior in sarcoma cells and identifies genes associated with metastasis

0423223 - ÚMG 2014 RIV US eng J - Journal Article
Kovářová, Denisa - Plachý, Jiří - Kosla, Jan - Trejbalová, Kateřina - Čermák, Vladimír - Hejnar, Jiří
Downregulation of HOPX controls metastatic behavior in sarcoma cells and identifies genes associated with metastasis.
Molecular Cancer Research. Roč. 11, č. 10 (2013), s. 1235-1247. ISSN 1541-7786. E-ISSN 1557-3125
R&D Projects: GA MŠMT(CZ) LC06061
Institutional support: RVO:68378050
Keywords : homeobox gene * metastasis * HOPX
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 4.502, year: 2013

Comparing the gene expression profiles of metastatic and nonmetastatic cells has the power to reveal candidate metastasis-associated genes, whose involvement in metastasis can be experimentally tested. In this study, differentially expressed genes were explored in the v-src-transformed metastatic cell line PR9692 and its nonmetastatic subclone PR9692-E9. First, the contribution of homeodomain only protein X (HOPX) in metastasis formation and development was assessed. HOPX-specific knockdown decreased HOPX expression in the nonmetastatic subclone and displayed reduced cell motility in vitro. Critically, HOPX knockdown decreased the in vivo metastatic capacity in a syngeneic animal model system. Genomic analyses identified a cadre of genes affected by HOPX knockdown that intersected significantly with genes previously found to be differentially expressed in metastatic versus nonmetastatic cells. Furthermore, 232 genes were found in both screens with at least a two-fold change in gene expression, and a number of high-confidence targets were validated for differential expression. Importantly, significant changes were demonstrated in the protein expression level of three metastatic-associated genes (NCAM, FOXG1, and ITGA4), and knockdown of one of the identified HOPX-regulated metastatic genes, ITGA4, showed marked inhibition of cell motility and metastasis formation. These data demonstrate that HOPX is a metastasis-associated gene and that its knockdown decreases the metastatic activity of v-src-transformed cells through altered gene expression patterns.
Permanent Link: http://hdl.handle.net/11104/0229370