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Abstract

Presence of a distinct population of cells that drives tumor progression supports the hierarchicalmodel of tumor development in Glioblastoma (GBM) and substantiates the cancer stemcell hypothesis. Amongst the various developmental signaling pathways that are aberrantly activated, we here show that activated Wnt/β-catenin signaling pathway plays a critical role in malignant transformation and tumor progression in gliomas. We demonstrate that Wnt ligands — Wnt1 and Wnt3a are expressed in a graded manner in these tumors as well as over-expressed in glioma stem cell-lines. A selective inhibition of Wnt signaling pathway by selective knock-down of its ligands Wnt1 andWnt3a in glioma-derived stem-like cells led to decreased cell proliferation, cell migration and chemo-resistance. Furthermore, Wnt silencing in glioma cells reduced the capacity to form intra-cranial tumors in vivo. Taken together, our study indicatesWnt/β-catenin signaling pathway as an essential driver of glioma tumorigenesis, recognizing role ofWnt3a as an oncogene and thereby offering novel therapeutic strategies for management of these tumors.

Item Type:	Article
Subjects:	Cancer Biology
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	13 Apr 2015 06:51
Last Modified:	03 Jul 2015 05:35
URI:	http://nccs.sciencecentral.in/id/eprint/56

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