The transcription factor EGR1 regulates metastatic potential of v-src transformed sarcoma cells.
Metastatic spreading of cancer cells is a highly complex process directed primarily by the interplay between tumor microenvironment, cell surface receptors, and actin cytoskeleton dynamics. To advance our understanding of metastatic cancer dissemination, we have developed a model system that is based on two v-src transformed chicken sarcoma cell lines-the highly metastatic parental PR9692 and a non-metastasizing but fully tumorigenic clonal derivative PR9692-E9. Oligonucleotide microarray analysis of both cell lines revealed that the gene encoding the transcription factor EGR1 was downregulated in the non-metastatic PR9692-E9 cells. Further investigation demonstrated that the introduction of exogenous EGR1 into PR9692-E9 cells restored their metastatic potential to a level indistinguishable from parental PR9692 cells. Microarray analysis of EGR1 reconstituted cells revealed the activation of genes that are crucial for actin cytoskeleton contractility (MYL9), filopodia formation (MYO10), the production of specific extracellular matrix components (HAS2, COL6A1-3) and other essential pro-metastatic abilities.
Cermák
Vladimír
V
Institute of Molecular Genetics AS CR, v.v.i. Vídenská 1083, Prague, Czech Republic.
Kosla
Jan
J
Plachý
Jirí
J
Trejbalová
Katerina
K
Hejnar
Jirí
J
Dvorák
Michal
M
D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D002645:Chickens; D003599:Cytoskeleton / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D007700:Kinetics; D009362:Neoplasm Metastasis / Q000235:genetics*; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology*
D051766:Early Growth Response Protein 1; D015688:Oncogene Protein pp60(v-src)