Reciprocal Activation of Transcription Factors Underlies the Dichotomy between Proliferation and Invasion of Glioma Cells

作者: Harshil D. Dhruv , Wendy S. McDonough Winslow , Brock Armstrong , Serdar Tuncali , Jenny Eschbacher

DOI: 10.1371/JOURNAL.PONE.0072134

关键词:

摘要: Histology of malignant glioma depicts dense proliferative areas rich in angiogenesis as well dissemination neoplastic cells into adjacent brain tissue. Although the mechanisms that trigger transition from to invasive phenotypes are complex, dichotomy cell proliferation and migration, "Go or Grow" hypothesis, argues for specific coordinated regulation these phenotypes. We investigated transcriptional elements accompany migration proliferation, consider therapeutic significance hypothesis. Interrogation matched core rim regions human glioblastoma biopsy specimens situ (n = 44) revealed higher (Ki67 labeling index) residing at compared rim. Profiling activated transcription factors a panel migration-activated versus migration-restricted GBM portrayed strong NF-κB activity migratory population. In contrast, increased c-Myc was found cells. Validation by NF-κB- c-Myc-driven GFP RFP, respectively, showed an active migrating cells, whereas proliferative, restricted displayed activity. Immunohistochemistry on clinical validated robust phosphorylated staining tumor core, detected Functional genomics depletion expression siRNA oligonucleotides reduced vitro, but surprisingly, enhanced significantly. Conversely, inhibition pharmacological inhibitors, SN50 BAY-11, decreased both vitro invasion ex vivo. Notably, have no effect rate These findings suggest reciprocal suppression/activation factors, such may underlie shift "growing-to-going" phenotype.

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