[HTML][HTML] SNAI2/Slug promotes growth and invasion in human gliomas

HW Yang, LG Menon, PM Black, RS Carroll… - BMC cancer, 2010 - Springer
HW Yang, LG Menon, PM Black, RS Carroll, MD Johnson
BMC cancer, 2010Springer
Background Numerous factors that contribute to malignant glioma invasion have been
identified, but the upstream genes coordinating this process are poorly known. Methods To
identify genes controlling glioma invasion, we used genome-wide mRNA expression profiles
of primary human glioblastomas to develop an expression-based rank ordering of 30
transcription factors that have previously been implicated in the regulation of invasion and
metastasis in cancer. Results Using this approach, we identified the oncogenic …
Background
Numerous factors that contribute to malignant glioma invasion have been identified, but the upstream genes coordinating this process are poorly known.
Methods
To identify genes controlling glioma invasion, we used genome-wide mRNA expression profiles of primary human glioblastomas to develop an expression-based rank ordering of 30 transcription factors that have previously been implicated in the regulation of invasion and metastasis in cancer.
Results
Using this approach, we identified the oncogenic transcriptional repressor, SNAI2/Slug, among the upper tenth percentile of invasion-related transcription factors overexpressed in glioblastomas. SNAI2 mRNA expression correlated with histologic grade and invasive phenotype in primary human glioma specimens, and was induced by EGF receptor activation in human glioblastoma cells. Overexpression of SNAI2/Slug increased glioblastoma cell proliferation and invasion in vitro and promoted angiogenesis and glioblastoma growth in vivo. Importantly, knockdown of endogenous SNAI2/Slug in glioblastoma cells decreased invasion and increased survival in a mouse intracranial human glioblastoma transplantation model.
Conclusion
This genome-scale approach has thus identified SNAI2/Slug as a regulator of growth and invasion in human gliomas.
Springer