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An excellent research work from SCU published in an authorized journal Cancer Cell

Date:2016-09-25

Fanghui Lu, a Ph.D. candidate in Sichuan University, recently published a research article titled with ”Olig2-Dependent Reciprocal Shift in PDGF and EGFReceptor Signaling Regulates Tumor Phenotype and Mitotic Growth in Malignant Glioma” in Cancer Cell, which is a top journal in Cancer field with high impact factor (23.523). The first author, Fanghui Lu, is from Laboratory of Pathology in West China Hospital, Sichuan University. Her advisor is Prof. Hong Bu. In 2011, she went to University of Texas Southwestern Medical Center and in 2013, shecontinued to do her study in Cincinnati Children’s Hospital Medical Center. This study is under the direction of Dr. Qing Lu, a visiting professor of our university.

Glioblastoma (GBM) is the most common malignant brain tumor in adults, exhibiting distinct molecular characteristics, while the underlying mechanism of tumor initiation and progression is not known yet. In this study, Lu et al. identified mitotic Olig2+ cells as glioma-propagating cells in gliomas by a cell suicide mouse model, elimination of which blocks tumor initiation and progression. Intriguingly, deletion of Olig2 resulted in tumors that grow, albeit at a decelerated rate, which further support the essential roles of Olig2 in gliomas. As well, using the next generation sequencing for genome occupancy and expression profiling analyses, they discovered that Olig2 directly activates cell proliferation machinery to promote tumorigenesis. Olig2 deletion causes a tumor phenotypic shift from an oligodendrogenesis-correlated proneural toward an astrocyte-associated classical gene expression pattern, manifest in down-regulation of PDGF receptor-alpha and reciprocal up-regulation of EGF receptor signaling. Olig2 deletion further sensitizes glioma cells to EGF receptor inhibitors and extends animal life spans. Thus, Olig2-orchestrated receptor signaling drives mitotic growth and regulates glioma phenotypic plasticity. Targeting Olig2 may circumvent resistance to EGFR-targeted drugs. The profound impact of targeting Olig2 and EGFR signaling on glioma formation illuminates an alternative avenue to stratify GBM treatment with tailored pharmacological intervention to inhibit the growth of these highly lethal malignant

brain tumors.

Figure from the preview article "Head of the Class: OLIG2 and Glioblastoma Phenotype" in Cancer Cell this issue:

Figure legend: Genomic mapping has driven the classification of glioblastoma into distinct molecular subclasses, but mechanisms that regulate tumor subclass phenotypes are only now emerging. In this issue of Cancer Cell, Lu et al. describe a phenotypic switch from PDGFRA-enriched “proneural” to EGFR-enriched “classical” features in glioblastoma upon ablation of Olig2.

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