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conferenceseries
.com
Volume 5, Issue 2 (Suppl)
Transcriptomics, an open access journal
ISSN: 2329-8936
Molecular Biology 2017
August 31-September 01, 2017
2
nd
International Conference on
August 31-September 01, 2017 Philadelphia, USA
Molecular Biology, Nucleic Acids &
Molecular Medicine
FOXO1/Sprouty-2 pathway inhibits endothelial cell tumor growth
Sriram Ayyaswamy
Texas Children’s Hospital, USA
Baylor College of Medicine, USA
V
ascular tumors are neoplasms of endothelial cell origin and have a wide spectrum of clinical presentations, ranging
from benign infantile hemangiomas in children to low-grade malignant hemangioendotheliomas and highly aggressive
angiosarcomas in adults. To date, the molecular basis of vascular tumor pathogenesis is poorly understood and standard
therapy for these tumors has limited clinical efficacy. Forkhead box protein O1 (
FOXO1
) is a transcription factor with tumor
suppressor function and is dysregulated in human cancer. In this study, we showed that
FOXO1
suppressed vascular tumor
growth, and mechanistically, the inhibitory effects of
FOXO1
are mediated by Sprouty2.
FOXO1
expression was reduced in
a variety of human vascular tumors examined. Knockdown of
FOXO1
gene expression with short hairpin RNA resulted in
increased vascular tumor cell migration and proliferation in vitro and in vivo animal models. Conversely, over-expression
of constitutively active
FOXO1
in these cells suppressed cell growth. We observed that
FOXO1
interacted with Sprouty2
promoter in situ in chromatin immunoprecipitation assay and increased Sprouty2 gene expression in tumor cells. Like FOXO1,
Sprouty2 expression was reduced in vascular tumors. Over-expression of Sprouty2 decreased tumor cell growth and migration.
Conversely, knockdown of Sprouty2 increased tumor growth in vitro and in vivo. Knockdown of Sprouty2 in cells with over-
expression of constitutively active
FOXO1
resulted in reduced tumor growth and rescued the
FOXO1
phenotype, indicating
that Sprouty2 is an important mediator of the biological effects of FOXO1. Microarray gene expression profiling of human
angiosarcoma cells with Sprouty2 knockdown together with network data integration using bioinformatics analysis revealed
important Sprouty2-regulated genes that are involved in angiogenesis, apoptosis and growth signal transduction pathways. In
summary, these findings demonstrate important growth regulatory role of the FOXO1/Sprouty2 pathway in endothelial cell
tumors and highlight the potential roles of novel pathways downstream of Sprouty2 in these lesions.
ayyaswam@bcm.eduTranscriptomics 2017, 5:2 (Suppl)
DOI: 10.4172/2329-8936-C1-013